The DOI matches its Crossref record; 200 of the 200 references it cites were found in a registry or an index; 97 of the 139 sources its claims cite were checked for support.
microRNA strand selection: Unwinding the rules
Open accessAbstract
microRNAs (miRNAs) play a central role in the regulation of gene expression by targeting specific mRNAs for degradation or translational repression. Each miRNA is post‐transcriptionally processed into a duplex comprising two strands. One of the two miRNA strands is selectively loaded into an Argonaute protein to form the miRNA‐Induced Silencing Complex (miRISC) in a process referred to as miRNA strand selection. The other strand is ejected from the complex and is subject to degradation. The target gene specificity of miRISC is determined by sequence complementarity between the Argonaute‐loaded miRNA strand and target mRNA. Each strand of the miRNA duplex has the capacity to be loaded into miRISC and possesses a unique seed sequence. Therefore, miRNA strand selection plays a defining role in dictating the specificity of miRISC toward its targets and provides a mechanism to alter gene expression in a switch‐like fashion. Aberrant strand selection can lead to altered gene regulation by miRISC and is observed in several human diseases including cancer. Previous and emerging data shape the rules governing miRNA strand selection and shed light on how these rules can be circumvented in various physiological and pathological contexts. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes how miRNA strand selection is governed mainly by 5′ nucleotide identity and the relative thermodynamic stability of miRNA duplex ends, and how these rules can be circumvented. It compiles miRBase data showing that many miRNAs deviate from these rules and discusses isomiRs, RNA modifications, Argonaute mutations, and disease-associated arm switching.
Key findings
- miRNA strand selection is primarily driven by two duplex-intrinsic features: the 5′ nucleotide of each strand, with a preference of U > A > C > G, and the relative thermodynamic stability of the two duplex ends. Human Ago2 MID domain binds UMP twice as strongly as AMP and approximately 30 times more strongly than CMP or GMP; guide strands commonly begin with U, passenger strands often with C.
- In the authors’ miRBase analysis, about half of miRNAs in each organism did not follow one of the two rules, and 17–25% did not follow either the 5′ nucleotide preference or thermodynamic stability rule: *C. elegans* (n = 189), *Drosophila* (n = 219), and humans (n = 832).
- Argonaute contributes directly to strand selection: in *C. elegans*, single amino acid substitutions in ALG-1 MID (G553R) and PIWI (G716E, S895F, S939F) domains reverse strand selection for certain miRNAs, but not all, and these mutations are not located within the guide RNA-binding pocket.
- Strand selection can be regulated by templated and nontemplated isomiRs, uridylation, A-to-I editing, and altered Dicer/TRBP processing; altered strand usage is associated with diseases including BRCA1/BAP1-deficient cancers with high miR-223* (5p), squamous cell carcinoma with both miR-21 and miR-21*, and atrial fibrillation with a miR-133 U–C point mutation.
Methods
- Narrative review of miRNA biogenesis, miRISC loading, strand selection mechanisms, regulation, and disease associations.
- For the original analysis, miRNA sequences and abundances were obtained from miRBase Release 22.1 for *C. elegans* (n = 189), *Drosophila melanogaster* (n = 219), and humans (n = 832); duplexes were assembled from the most abundant 5p and 3p reads using RNAduplex from ViennaRNA package v2.4.14, excluding extremely low-abundance miRNAs and those with ambiguous arm preference.
- Rule violations were defined as: passenger 5′ nucleotide equal to or more preferred than the guide 5′ nucleotide (preference U > A > C > G), or guide-end thermodynamic stability equal to or higher than passenger-end stability, using the terminal four base pairs and ΔΔG = Δguide − Δpassenger.
Limitations
- The paper states that much of the data used to formulate the rules of miRNA strand selection came from in vitro experiments, and how well these rules hold in a living organism throughout its lifespan is yet to be established.
- The paper states that its miRBase analysis uses the most highly expressed 5p and 3p strands without considering isomiRs, assumes the most abundant 5p and 3p reads originate from the same duplex, cannot exclude that they originate from distinct duplexes, and notes that miRBase annotations or abundances may not accurately reflect tissue-dependent miRNA expression.
- Evident from the text: as a review, it reports no new experimental validation of strand selection in vivo; disease and regulatory mechanisms are largely based on cited studies, and Table 1 contains missing or not-assessed entries that limit quantitative synthesis.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
39 Own interpretation · 35 Supported · 28 Partly supported · 12 No basis given · 9 Sources not found · 8 No full text of the sources · 7 Not checked yet · 5 Supported so far · 3 Own result · 1 Not supported · 1 Couldn’t confirm · 1 Own method · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, in some cases, both arms of the duplex give rise to functional mature miRNAs that are loaded into Argonaute proteins to regulate gene expression (Ghildiyal, Xu, Seitz, Weng, & Zamore, 2009; Okamura, Liu, & Lai, 2009).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
What the sources say
- Supportedcites Ghildiyal, Xu, Seitz, Weng, & Zamore, 2009 source
In “Sorting combines structure and sequence information,” the paper says that some pre-miRNAs produce functional small RNAs from both arms. It reports that the two strands load into distinct Argonaute proteins and suggests that Ago2-loaded miRNA* strands regulate target RNAs. (LLM, conf=0.90)
- Supportedcites Okamura, Liu, & Lai, 2009 source
The Results section on AGO2-loaded miRNA* species reports that both strands of miR-276a are active in S2 cells, as shown by their effects on cognate target reporters. The Results also report preferential loading of mature and star strands into different Argonaute complexes. The demonstrated target regulation is in reporter assays. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Obvious miRNA duplex‐intrinsic factors, such as 5′ nt identity or end stability, were not able to distinguish the strand switching‐miRNAs from miRNAs resistant to ALG‐1 mutations (Zinovyeva et al., 2015).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Zinovyeva et al., 2015 source
The section on microRNAs with grossly abnormal miR* loading reports that class I microRNAs had no 5′ nucleotide bias and that duplex and end energies did not distinguish them from the other classes. It also says that 5′ pairing and seed-energy differences did not explain or distinguish their loading patterns. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Furthermore, the phosphate moiety of the 5′ nucleotide of the guide strand, but not the passenger strand, is required for miRISC loading of the miRNA guide strand in fly embryonic lysates (Kawamata, Yoda, & Tomari, 2011).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Kawamata, Yoda, & Tomari, 2011 source
The Results and Discussion section ('RISC loading requires 5′ phosphate of the guide') concludes that the guide-strand 5′ phosphate is required for RISC loading, while the passenger-strand phosphate is dispensable. The same section identifies the assay material as overnight embryo lysate from flies. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Consistently, in C. elegans, single amino acid substitutions within the MID (G553R) and PIWI (G716E, S895F, and S939F) domains of the miRNA Argonaute ALG‐1 (Argonaute‐like Gene) reverse the strand selection of certain miRNAs (Zinovyeva, Bouasker, Simard, Hammell, & Ambros, 2014; Zinovyeva, Veksler‐Lublinsky, Vashisht, Wohlschlegel, & Ambros, 2015).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Zinovyeva et al., 2014 sourceExperimental — accuracy not yet measured
The Results sections on alg-1 missense mutations and pre-microRNA processing describe four ALG-1 substitutions and locate affected residues in Argonaute domains. But the paper does not report that these substitutions reverse strand selection for any miRNA; its RNA-duplex experiments instead test loading and passenger-strand cleavage. Thus it supports the mutations, not the attributed strand-selection effect. (LLM, conf=0.84)
- Partly supportedcites Zinovyeva et al., 2015 sourceExperimental — accuracy not yet measured
The Results report that ALG-1(ma192) and ALG-1(ma202) affect the PIWI and MID domains, respectively. The strand-selection analysis reports that miR-2* can be loaded into mutant ALG-1 in the guide-strand configuration, supporting altered strand choice for some miRNAs. Our copy does not identify these mutants by the four specified amino acid substitutions or establish strand-selection reversal for each substitution. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Additional modifications that modify the ribose sugar group or substitution modifications to the 2′ hydroxyl group of the ribose can also affect TS of the siRNA duplex and influence strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Bramsen et al., 2009 source
The Results (page unavailable) identify both 2′-substituted RNAs and modifications of the ribose sugar ring among the chemistries tested. In “Destabilization of SS 3′-ends enhances silencing efficiency” (page unavailable), the paper reports that these modifications can stabilize or destabilize the duplex and that changes to its thermodynamic profile can favor incorporation of one strand into RISC. (LLM, conf=0.91)
- Not matchedcites Bramsen & Kjems, 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Ui-Tei et al., 2012 sourceExperimental — accuracy not yet measured
In “Thermodynamic Control of RNA Strand Incorporation into the RISC by Chemical Modifications” (page unavailable), the paper says duplex thermodynamics affect guide-strand selection; Table 2 specifically reports that the ribose modification 4′-thioribonucleoside increases stability and enhances selective guide-strand loading. The paper discusses 2′-O-methyl and 2′-deoxy modifications in relation to off-target effects and seed-region stability, but does not establish that those 2′-hydroxyl substitutions affect siRNA duplex stability and strand selection. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“miR‐144* (5p) expression is down‐regulated in nonsmall cell lung cancer (NSCLC) (Song et al., 2018), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Song et al., 2018 source
Results §3.1 reports significantly lower miR-144-5p expression in NSCLC adenocarcinoma and squamous-cell carcinoma specimens than in normal lung tissue, and lower expression in NSCLC cell lines than in normal airway epithelial cells. The Discussion likewise states that miR-144-5p was downregulated in NSCLC specimens and cell lines. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In particular, chemical modifications that affect the 5′ end stability of the siRNA duplex can affect the relative TS of each end and lead to a reversal in siRNA strand selection (Bramsen et al., 2009; Bramsen & Kjems, 2013; Ui‐Tei, Nishi, Takahashi, & Nagasawa, 2012).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Bramsen et al., 2009 source
The Discussion states that the strand with the less stable 5′ end is preferentially selected as the guide strand and that chemical modifications can change this thermodynamic asymmetry. The Results further report that destabilizing the sense strand’s 5′ end should disfavor antisense-strand incorporation, supporting the claimed possibility of a reversal in strand preference. Page numbers are not available in our copy. (LLM, conf=0.88)
- Not matchedcites Bramsen & Kjems, 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Ui-Tei, Nishi, Takahashi, & Nagasawa, 2012 sourceExperimental — accuracy not yet measured
The section “Thermodynamic Control of RNA Strand Incorporation into the RISC by Chemical Modifications” (page not available) says that 5′-end stability influences which strand enters RISC and that chemical modifications can increase selective guide-strand loading. It does not report a reversal in strand selection, so that specific outcome is not established by our copy. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The miR‐24‐2* (5p) strand is upregulated in MCF‐7 breast cancer cell lines compared to control mammary epithelial cells (Martin et al., 2012), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Martin et al., 2012 source
The Introduction states that miR-24-2*, the passenger strand, is increased in MCF-7 breast cancer cells compared with non-malignant mammary epithelia. The Results section repeats that comparison. The paper reports the comparison while citing earlier work for it. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, isomiRs resulting from altered Dicer processing sites have been shown to change the thermodynamic properties of mammalian miRNAs, leading to reversed strand selection (Lee & Doudna, 2012; Wilson & Doudna, 2014).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Lee & Doudna, 2012 sourceExperimental — accuracy not yet measured
The section “Functional effects of differential cleavage upon TRBP association” reports that a shifted Dicer cleavage product changed guide-strand activity in human cells and proposes altered duplex-end stability as an explanation. It does not show reversed strand selection: the original product favored miR-200a-3p, whereas the altered product allowed both strands to function to a similar extent. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Could not verifycites Wilson & Doudna, 2014 sourceExperimental — accuracy not yet measured
The paper's text (Biophysical Journal supplement, p. 1463a; no section label in our copy) discusses a hypothesized role for TRBP in strand selection and experiments on the Dicer–TRBP interface. Searches for altered Dicer processing sites and thermodynamic asymmetry found no passage addressing isomiRs, changed miRNA thermodynamics, or reversed strand selection. (LLM, conf=0.75)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“An early observation in mice found that the relative expression of 5p and 3p strands varied for certain miRNA duplexes across different tissues (Ro, Park, Young, Sanders, & Yan, 2007).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Ro, Park, Young, Sanders, & Yan, 2007 source
In Results and Discussion, under “Validation and expression profiling of paired mouse miRNAs,” the paper reports that both strands of mir-194 accumulated in some mouse tissues, while only the 5p strand accumulated in others. This directly supports the claim that the relative expression of 5p and 3p strands varied across tissues. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, the strand bias of miR‐193a appears to be altered in breast cancer cell lines, as well as patient tissues (Tsai et al., 2016).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Tsai et al., 2016 source
The Results section, “Different arm expression preferences of miR-193a in breast cancer” (page unavailable), reports a significantly changed miR-193a-5p/miR-193a-3p ratio in breast cancer tissues versus adjacent normal tissues. The Results also describe altered arm expression preference in breast cancer cells, supporting the citing sentence’s hedged description of strand bias in cell lines and patient tissues. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, TUT4/TUT7 expression levels appear to be regulated in developmental and tissue‐specific fashions, suggesting that regulation of TUT4/TUT7 activity can dictate strand selection of miR‐324 in humans, resulting in arm switching across tissues (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Kim et al., 2020 source
The paper’s proposed model (pp. 20–21 of our copy) explicitly says TUT4/7 levels are subject to tissue- and developmental-stage-specific regulation and that the miR-324 arm ratio changes accordingly. Its results also report differences in TUT4/7 levels across mouse tissues (Figure 2B). (LLM, conf=0.93)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“have recently been shown to affect strand selection of human miR‐324 (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Kim et al., 2020 source
In the section “miR-324 arm switching is controlled by TUT4 and TUT7” (page not supplied), TUT4/7 knockdown in human HEK293T cells changed the relative abundance of miR-324 strand isoforms. This supports the claim that TUT4/TUT7 affect strand selection of human miR-324. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“TDMD may promote dissociation of the 3′ end of the miRNA from the Argonaute protein, thereby exposing the 3′ end to modifications that lead to miRNA degradation (Sheu‐Gruttadauria et al., 2019; Yang et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Sheu-Gruttadauria et al., 2019 source
The Results section ('Disruption of 3′-end miRNA binding by Ago') says TDMD targets induce stable removal of the miRNA 3′ end from Ago’s PAZ domain, making it susceptible to enzymatic attack and destruction. The Introduction also describes the 3′ end being released from its binding pocket and exposed for enzymatic attack. The claim’s 'may' is consistent with these findings. (LLM, conf=0.94)
- Supportedcites Yang et al., 2020 source
The Introduction states that, during TDMD, pairing with a target promotes dislocation of the miRNA’s 3′ end from AGO, making it accessible to enzymatic modifications. The Discussion’s Fig. 7 model links exposure of that end to modifications that can lead to miRNA decay. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A‐to‐I editing has been shown to influence miRNA strand selection in mice and human cells (Iizasa et al., 2010; Li et al., 2017).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Iizasa et al., 2010 sourceExperimental — accuracy not yet measured
The Results report that editing reduces loading of the miR-BART6-5p strand into miRISC, while 5p remains the major effective strand. The Methods describe an assay using a complex from human HEK293 cells, but the paper does not show an effect in mice or a switch in which strand is selected. Section labels are available in our copy, but page numbers are not. (LLM, conf=0.86)
- Not matchedcites Li et al., 2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The expression of isomiRs appears to be regulated in a developmental and tissue‐specific manner (Fernández‐Pérez, Brieño‐Enríquez, Isoler‐Alcaraz, Larriba, & del Mazo, 2017; Fernandez‐Valverde, Taft, & Mattick, 2010; Woldemariam et al., 2019; Wyman et al., 2011).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Fernández‐Pérez, Brieño‐Enríquez, Isoler‐Alcaraz, Larriba, & del Mazo, 2017 source
The Discussion (‘Role of isomiRs and nontemplate additions in developing gonads’) says isomiRs were differentially regulated across developmental samples: gonadal somatic cells had a more stable profile, while primordial germ cells were more variable. The Results (‘Differential production of isomiRs during gonadal development’) identify stage-specific changes at E12.5 and in female germ cells at E13.5. This supports the hedged claim in the mouse gonadal cells studied. (LLM, conf=0.89)
- Supportedcites Fernandez‐Valverde, Taft, & Mattick, 2010 source
The Discussion reports that the size of at least eight mature miRNAs changes with developmental stage or tissue and says the reproducible expression of these isomiRs suggests biological regulation. It also describes distinct isomiR patterns in early development and adult tissues, supporting the claim’s cautious wording. (LLM, conf=0.94)
- Could not verifycites Woldemariam et al., 2019 sourceExperimental — accuracy not yet measured
Results §3.2.2 identifies isomiR variants, but does not describe their expression across tissues or developmental stages. Results §3.3 reports tissue- and stage-associated patterns for miRNAs, not specifically isomiRs; it also says the authors could not compare expression differences between developmental stages. Searches for isomiR expression across tissues and stages found no passage establishing the attributed claim. (LLM, conf=0.74)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
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In the paper
“In other examples, a G/C polymorphism in the miR‐146a locus, associated with papillary thyroid carcinoma (PTC) progression, alters the sequence of miR‐146a* (3p) strand, and likely leads to changes in target repression, contributing to PTC (Jazdzewski et al., 2009; Labbaye & Testa, 2012), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not checked yetcites Jazdzewski et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
- Partly supportedcites Labbaye & Testa, 2012 sourceExperimental — accuracy not yet measured
The “miR-146a and cancer” section reports that the G/C polymorphism is associated with increased risk of acquiring papillary thyroid carcinoma, specifically in GC heterozygotes. It discusses predisposition to cancer development, but does not establish an association with progression of existing PTC. Page numbers are unavailable in our copy. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not checked yet
Every source the paper cites for this claim was checked and supports it.
In the paper
“Cancer cells lacking BRCA1 (breast cancer 1) and BAP1 (BRCA1‐associated protein), which are deficient in homologous recombination, aberrantly express high levels of miR‐223* (5p) (Srinivasan et al., 2019; Figure 6b, Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Srinivasan et al., 2019 source
The Results section ('MiR223-3p Induces Synthetic Lethality in HR-Deficient Cancers'; page unavailable) says BRCA1 and BAP1 are required for homologous recombination. It reports that all BRCA1- and BAP1-deficient cancer cells tested suppressed miR223-3p and instead processed miR223-5p to maturity, opposite to the HR-proficient cell lines examined. This supports the claim as a comparison of the tested cell lines. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, mammalian Dicer is dispensable for asymmetric miRNA strand selection in vitro (Betancur & Tomari, 2011; Murchison, Partridge, Tam, Cheloufi, & Hannon, 2005)”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Betancur & Tomari, 2011 sourceExperimental — accuracy not yet measured
The in vitro assays for asymmetric RISC assembly (page unavailable) found that Dicer was dispensable for asymmetric strand loading, but tested a let-7-based siRNA duplex, not a miRNA/miRNA*-like duplex. The miRNA/miRNA*-like duplex was tested in the in vivo reporter assays (page unavailable). Thus the paper supports Dicer-independent asymmetric selection, but not the claim's combination of miRNA strand selection and in vitro testing. (LLM, conf=0.87)
- Partly supportedcites Murchison, Partridge, Tam, Cheloufi, & Hannon, 2005 sourceExperimental — accuracy not yet measured
The Results report that siRNAs entered RISC and functioned in cultured Dicer-null mouse embryonic stem cells, and the Discussion says these cells retained the ability to incorporate siRNAs into RISC. The paper does not establish that Dicer is dispensable for asymmetric miRNA strand selection; its Results instead report an absence of mature miRNAs in the Dicer-deficient cells. Page numbers were not available in our copy. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“High expression of miR‐574* (5p) is associated with advanced gastric cancer stages (Zhang et al., 2019).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Zhang et al., 2019 source
The Results section, “miR-574-5p/-3p ratio is correlated with GC progression,” directly reports that higher miR-574-5p levels were correlated with more advanced gastric cancer stages (III/IV versus I/II; p = 0.0028). (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In another example, Drosophila ethanol exposure leads to the accumulation of certain miR passenger strands (Ghezzi, Zomeno, Pietrzykowski, & Atkinson, 2016).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Ghezzi, Zomeno, Pietrzykowski, & Atkinson, 2016 source
The Discussion reports significant accumulation changes in four ethanol-responsive miRNA* strands presumed to be passenger strands. The Results describe the comparison between ethanol-exposed and untreated Drosophila, supporting the claim that ethanol exposure affects these strands. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, these variations can also influence the relative TS of miRNA duplex ends (Lee & Doudna, 2012; Starega‐Roslan, Koscianska, Kozlowski, & Krzyzosiak, 2011).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Lee & Doudna, 2012 source
In “Functional effects of differential cleavage upon TRBP association” (page not provided), the paper says changes in product duplex length can change the relative stability of its ends. This supports the claim that the variations can influence relative thermodynamic stability (TS). (LLM, conf=0.91)
- Not matchedcites Starega‐Roslan, Koscianska, Kozlowski, & Krzyzosiak, 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, Argonaute phosphorylation within its 5′ nucleotide binding pocket influences its ability to bind the guide strands of several miRNAs (Rüdel et al., 2010)”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Rüdel et al., 2010 source
The Results identify phosphorylated Ago2 Y529 within the small-RNA 5′-end-binding pocket. In the Results section on small-RNA binding, a mutation mimicking phosphorylation markedly reduced Ago2 binding to three endogenous miRNAs (miR-19b, miR-16 and miR-25). The paper presents phosphorylation’s effect on binding as an inference from that experiment, consistent with the claim’s wording. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, this effect is not equal—reduction of xrn‐1 or xrn‐2 have been shown to affect the 5p/3p ratios of certain miRNAs (Chatterjee et al., 2011; Miki, Rüegger, Gaidatzis, Stadler, & Großhans, 2014).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Chatterjee et al., 2011 source
The Introduction (page not available) says that depletion of either xrn-1 or xrn-2 can cause certain miRNA passenger strands to accumulate. The paper also reports accumulation of selected passenger strands after XRN-1 or XRN-2 depletion (Figures 4B–4C), supporting a change in the relative abundance of the two strands—the claimed 5p/3p ratios. (LLM, conf=0.90)
- Supportedcites Miki, Rüegger, Gaidatzis, Stadler, & Großhans, 2014 source
The Results section, “Specific miRNAs are stabilized on XRN2 inactivation” (page unavailable), reports that miR-87 decay was delayed when xrn-2 was inactivated, while its opposite-arm strand, miR-87*, continued to decay rapidly. That differential effect supports the xrn-2 portion of the 5p/3p-ratio claim; the separately cited Chatterjee paper is offered for xrn-1. (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, changes in Dicer processing sites produce isomiRs with altered thermodynamic end stabilities that reverse strand selection of mammalian miRNAs in vitro (Kim et al., 2014; Lee & Doudna, 2012; Wilson & Doudna, 2014; Figure 4d).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Kim et al., 2014 sourceExperimental — accuracy not yet measured
The Results report that altered Dicer cleavage generates iso-miRs with changed thermodynamic stability and demonstrate altered strand selection in human cells. They describe the earlier miR-200a work as a demonstration of this possibility, but do not establish that the strand-selection reversal in this paper occurred in vitro; its own demonstration was in cells. (LLM, conf=0.86)
- Partly supportedcites Lee & Doudna, 2012 sourceExperimental — accuracy not yet measured
The isomiR-production section reports that Dicer–TRBP shifts the pre-miR-200a cleavage site, producing longer isomiRs in vitro. The functional-effects section links the altered products to end stability and guide-strand selection, but reports a change from strong 3p preference to similar use of both strands—not a reversal. Strand activity was tested with a reporter assay in human cells, rather than in vitro. (LLM, conf=0.89)
- Could not verifycites Wilson & Doudna, 2014 sourceExperimental — accuracy not yet measured
The available article text (no section or page supplied) discusses a hypothesized role for TRBP in strand selection and experiments disrupting the Dicer–TRBP interaction. It does not address changed Dicer processing sites, isomiR end stabilities, or reversal of strand selection in vitro; searches for those terms found no supporting passage. (LLM, conf=0.73)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“numerous miRNAs undergo arm switching in cancers (Chen et al., 2018).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Chen et al., 2018 source
The Discussion reports 51 pre-miRNAs displaying arm switching across different cancer types. The Results section on tumour versus tumour-adjacent tissue also lists several miRNAs that arm-switched in multiple tumours, supporting the claim that numerous miRNAs undergo arm switching in cancers. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Nucleotide compositions of the overhangs have been reported to affect TS of miRNA duplexes in vitro (Miller, Jones, Giovannitti, Piper, & Serra, 2008; O'Toole, Miller, Haines, Zink, & Serra, 2006), therefore altered nucleotide compositions of the overhangs may potentially alter strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Miller, Jones, Giovannitti, Piper, & Serra, 2008 sourceExperimental — accuracy not yet measured
The Abstract reports that overhang sequence affects the stability of experimentally studied RNA duplexes designed to mimic miRNA structures. It does not report thermodynamic measurements of actual miRNA duplexes, so the claim is more specific than the evidence. (LLM, conf=0.82)
- Not matchedcites O'Toole, Miller, Haines, Zink, & Serra, 2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Most miRNA duplexes contain two nucleotide overhangs at their 3′ ends.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Further, depletion or reduction of the 5′ ➔ 3′ exonucleases xrn‐1 and xrn‐2 result in accumulation of specific miRNAs and miR* strands (Chatterjee et al., 2011).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Chatterjee et al., 2011 source
The Introduction states that depletion of xrn-1 or xrn-2 can cause certain miR* passenger strands to accumulate. The passage on miRNA turnover (labeled Abstract in our copy) also reports accumulation of miRNA guide strands after xrn-1 depletion, while the TMMP passage reports upregulation of let-7(n2853) after depletion of either RNase. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TUT4 and TUT7, which uridylate let‐7 in an evolutionarily conserved manner (Chang, Triboulet, Thornton, & Gregory, 2013; Hagan, Piskounova, & Gregory, 2009; Heo et al., 2009; Lehrbach et al., 2009; Thornton, Chang, Piskounova, & Gregory, 2012; Wynsberghe et al., 2011), have recently been shown to affect strand selection of human miR‐324 (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Chang, Triboulet, Thornton, & Gregory, 2013 sourceExperimental — accuracy not yet measured
The paper’s discussion of the Lin28 pathway (indexed under Abstract; no page supplied) identifies Zcchc11 (TUT4) and Zcchc6 (TUT7) as enzymes that add oligouridine tails to pre-let-7. Our copy does not establish that this uridylation is evolutionarily conserved. (LLM, conf=0.85)
- Partly supportedcites Hagan, Piskounova, & Gregory, 2009 sourceExperimental — accuracy not yet measured
The Results identify Zcchc11 as a TUTase that uridylates pre-let-7 in mouse embryonic stem cells. The Discussion describes a homologous pathway in C. elegans as evidence that the mechanism is evolutionarily conserved. Our copy does not identify TUT7 or show that both named enzymes uridylate let-7. (LLM, conf=0.88)
- Partly supportedcites Heo et al., 2009 sourceExperimental — accuracy not yet measured
The Results show that TUT4 uridylates pre-let-7. They report only a weak reaction signal for TUTase7, with no significant effect on let-7 levels after depletion, and do not establish that both enzymes uridylate let-7 in an evolutionarily conserved manner (page not provided). (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“One major example is the nontemplated addition of uracil to the 3′ end of a miRNA strand that is catalyzed by 3′ terminal uridyl transferase (TUT) enzymes (reviewed in Menezes, Balzeau, & Hagan, 2018; Pirouz, Ebrahimi, & Gregory, 2019).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Menezes, Balzeau, & Hagan, 2018 source
The “MicroRNAs and uridylation” section describes adding non-templated uridine to the 3′ end of microRNAs. The Introduction identifies terminal uridylyl transferases (TUTases) as the enzymes responsible for 3′ RNA uridylation. (LLM, conf=0.93)
- Not matchedcites Pirouz, Ebrahimi, & Gregory, 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In gastric cancer, both arms of miR‐574, miR‐219 and miR‐369 are readily detectable (Zhang et al., 2019), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Zhang et al., 2019 source
The Results section ('miRNA arms show differential expression pattern in GC patients') explicitly says that both arms of miR-574, miR-219, and miR-369 can be simultaneously detected in gastric cancer tissues. It also reports examining the expression of all three pairs of arms in those tissues. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“miR‐144* (5p) directly targets ATF2, and it is possible that increased ATF2 levels upon reduced miR‐144* (5p) activity contributes to progression of NSCLC (Song et al., 2018).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Song et al., 2018 source
The Results (§3.4) report that miR-144-5p inhibited a reporter carrying the wild-type ATF2 3′UTR but not one with a mutated binding site. The Discussion (§4) explicitly identifies ATF2 as a direct target of miR-144-5p. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, Drosha and Dicer appear to generate 5′ and 3′ isomiRs at similar frequencies (Seitz et al., 2008)”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Seitz et al., 2008 sourceExperimental — accuracy not yet measured
The Results and Discussion proposes that Drosha and Dicer may generate 5′ and 3′ ends with similar, imperfect accuracy, and reports that Ago2 loading increases the apparent precision of 5′ ends. It does not establish that the enzymes generate 5′ and 3′ isomiRs at similar frequencies; that remains a proposed explanation rather than a measured frequency comparison. (LLM, conf=0.78)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recently, uridylation of miR‐324 by TUT‐4/7 was shown to directly influence the arm switching of miR‐324 (Kim et al., 2020, Figure 4c, Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Kim et al., 2020 source
The section “miR-324 arm switching is controlled by TUT4 and TUT7” reports that TUT4/7 knockdown reduced miR-324 uridylation and changed the ratio of its 5p and 3p isoforms. The Discussion explains the mechanism: TUT4/7 uridylate pre-miR-324, altering DICER cleavage and strand selection. The precise target of uridylation is the precursor, pre-miR-324. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Notable is a recent study providing a direct molecular mechanism for miR‐324 arm switching through uridylation and subsequent alternative Dicer processing (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
What the sources say
- Supportedcites Kim et al., 2020 source
The Discussion describes TUT4/7 uridylating pre-miR-324, followed by cleavage at an alternative DICER site and production of a duplex loaded in an inverted orientation. The section ‘Alternative DICER processing leads to arm switching’ and the concluding passage at 16/51 connect that processing to miR-324 arm switching. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strikingly, 17–25% of miRNA duplexes did not follow either the 5′ nt preference or TS rules (Figures 3a–c).”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The most abundant 5p and 3p miRNA strands originate from the same duplex.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In each organism that we examined, half of all miRNAs did not follow one of the two rules for miRNA strand selection (Figure 3a–c).”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The most abundant 5p and 3p miRNA strands originate from the same duplex.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At first glance, a significant number of miRNAs do not follow either the 5′ nucleotide or TS rules (see Figure 3).”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition to favoring a 5′ mono‐phosphorylated Uracil, Argonaute also appears to favor loading the end of the duplex that contains the lower relative thermodynamic stability.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As the miRNA strand selected for Argonaute loading directly determines the mRNA targets, altered strand selection can direct miRISC to repress a different set of target genes (Figure 2b).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“in vitro titration experiments found that the MID domain of human Ago2, a major miRNA‐associated Argonaute, binds to UMP twice as strongly as AMP and approximately 30 times more strongly than CMP or GMP (Frank et al., 2010).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Frank et al., 2010 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Structural analysis of human Ago2, an Argonaute associated with miRNAs, revealed that the 5′ nucleotide binding pocket shows a strong preference for Uracil (Frank et al., 2010.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Frank et al., 2010 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, Argonaute may directly sense the two major drivers of miRNA strand selection: thermodynamic end stability and 5′ nucleotide identity.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Major factors contributing to miRNA strand selection are two intrinsic features of the miRNA duplex: the identities of the 5′ nucleotide (nt) of each strand and the relative thermodynamic stability (TS) of the two ends of the duplex (Figure 2c).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“miRNA duplexes also contain mismatches; however, the presence and positions of central mismatches do not appear to play a substantial role in miRNA strand selection in human cells (Suzuki et al., 2015).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Suzuki et al., 2015 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, increasing the duplex‐end stability of the 5′ miRNA end or decreasing the duplex‐end stability of the 3′ end may now favor duplex unwinding from the 5′ end of the typically less abundant miR strand, resulting in duplex loading in the opposite orientation (Figure 4b).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, cells expressing mRNAs with miR* target sites may lead to stabilization of miR* strands, resulting in the 5p/3p ratio change without altering the preference of Argonaute for selecting the miR strand.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It is important to note that much of the data used to formulate the rules of miRNA strand selection were derived from in vitro experiments.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and there is some evidence suggesting that DNA damage influences strand selection of certain miRNAs (Tarasov et al., 2016).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not matchedcites Tarasov et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“miR‐223 (3p) directly targets components of the nonhomologous end‐joining (NHEJ) pathway.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, there are conflicting reports of whether Dicer plays a direct role in miRNA strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Specifically, mice brain tissue lacking Adenosine Deaminases Acting on RNA (ADAR, Adarb1 knockout) enzymes exhibit reversed strand selection for some of the miRNAs (Li et al., 2017).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not matchedcites Li et al., 2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Interestingly, A‐to‐I editing events are barely detectable in the mouse early embryo (Li et al., 2017) suggesting that A‐to‐I editing might regulate strand selection in a developmental and/or tissue specific manner.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not matchedcites Li et al., 2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“suggesting that A‐to‐I editing might regulate strand selection in a developmental and/or tissue specific manner.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not matchedcites Li et al., 2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to the hypothesized role of templated isomiRs, nontemplated isomiRs play a role in miRNA strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Environmental factors have also been observed to influence miRNA strand selection.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even a single base truncation or extension on the 5′ end of a miRNA strand can change the identity of the 5′ nucleotide of that strand.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, while the physiological significance of these mutations is unclear, collectively, these findings support the notion that, in principle, regulatory modifications to miRNA duplexes may play some role in miRNA strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the large population of miRNAs where relative strand abundance cannot be explained by either rule suggests that alternative mechanisms may regulate or contribute to strand selection of those miRNAs.”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we note that miRNA arm switching may not always be due to changes in miRNA strand selection per se.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For these miRNAs, if the 5′ nucleotide and the TS rules were the only determinants of strand selection, we would expect the miR* strand to be selected over the miR strand.”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While changes in miRNA strand abundance can result from several different mechanisms, we propose that altered miRNA strand selection is likely a major mechanism leading to miRNA arm switching (Figure 5).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Introducing mismatches into siRNA duplexes at certain positions of the passenger strand was found to further drive selection of the guide strand (Wu et al., 2011).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not matchedcites Wu et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“therefore altered nucleotide compositions of the overhangs may potentially alter strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Most miRNA duplexes contain two nucleotide overhangs at their 3′ ends.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are many examples and several reported mechanisms by which de‐regulation of miRNA strand selection becomes associated with human disease.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“and fly Dcr‐1 is not required for incorporation of miRNA::miRNA* duplexes into Ago1/miRISC (Kawamata, Seitz, & Tomari, 2009; Yoda et al., 2009).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Kawamata, Seitz, & Tomari, 2009 source
- Not matchedcites Yoda et al., 2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such alteration can remove a preferred 5′ nucleotide from a miR strand or add a favored 5′ nucleotide to a miR* strand, thereby shifting strand selection in favor of the miR* strand (Figure 4b).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strand selection appears to be mainly driven by two duplex‐intrinsic rules: miRNA 5′ nucleotide identity and the relative TS of duplex ends.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“TUT‐4/7 uridylate the 3p arm of miR‐324 leading to selection of the miR‐324* (3p) strand instead of the miR‐324 (5p) strand.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When regulated, it provides a mechanism to dramatically alter broad suites of distinct target genes.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miRNA strand selection as part of miRISC programming is a critical event that ultimately dictates target gene identity.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: unclear — It is unclear why the paper says it holds.
In the paper
“The oncogenicity of miR‐21* (3p) is mediated via its target gene, phosphatase, and actin regulator 4 (PPACTR4; Ge et al., 2015).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not matchedcites Ge et al., 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the analysis is limited, using the most highly expressed 5p and 3p strands for a given miRNA without taking isomiRs into consideration.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 58
- Probably not a substantial claim. 28
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“miR‐574* (5p) is oncogenic in colorectal cancer, NSCLC, and PTC (Cui, Tang, Chen, & Wang, 2014; Ji et al., 2012; Ma et al., 2016; X. Wang, Lu, Geng, Yang, & Shi, 2017; Zhou et al., 2015; Zhou et al., 2016), while miR‐574 (3p) is tumor suppressive in breast cancer and leukemia (Chiyomaru et al., 2013; Ujihira et al., 2015; Xu et al., 2020; Yao, Wu, Lindner, & Fox, 2017).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Disputedcites Cui, Tang, Chen, & Wang, 2014 sourceExperimental — accuracy not yet measured
Cui et al.’s Results report that reducing miR-574-5p increased proliferation and invasion in colorectal cancer cells, while increasing it had the opposite effect. The Discussion concludes that miR-574-5p plays a suppressive role in colorectal cancer liver metastasis, contrary to the oncogenic role attributed to this paper. The Discussion also mentions an earlier study reporting reduced tumor growth after miR-574-5p inhibition, but that is not Cui et al.’s finding. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Not matchedcites Ji et al., 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Ma et al., 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Consistent with this idea, the less abundant miR* strands were shown repress mRNAs containing predicted miR* target sites in flies and mammals, suggesting that miR* strands are functional (Okamura et al., 2008; Yang et al., 2010).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
What the sources say
- Not checked — no full text of the sourcecites Okamura et al., 2008 source
- Supportedcites Yang et al., 2010 source
The Abstract reports transcriptome-wide repression of seed-matched targets by star strands and direct repression of five miR-19* targets through star-seed sites. The Introduction also describes detectable miRNA* effects on target networks in Drosophila, while identifying the paper’s own tests as vertebrate work. (LLM, conf=0.91)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, these ALG‐1 mutations do not reverse strand selection for all miRNAs, suggesting that additional intrinsic or extrinsic factors may affect C. elegans miRNA strand selection differently for distinct miRNAs (Zinovyeva et al., 2015).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Zinovyeva et al., 2015 source
The Discussion reports that ALG-1 mutations affect strand selection differently depending on the particular microRNA. It also raises the possibility that microRNA features or additional extrinsic mechanisms influence which strand is selected, matching the citing sentence's qualified interpretation. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“microRNAs (miRNAs) play a central role in the regulation of gene expression by targeting specific mRNAs for degradation or translational repression.”
§ microRNA strand selection: Unwinding the rules > Abstract
What the sources say
- Supportedcites Bartel, 2018 source
The Introduction describes miRNAs as regulatory RNAs with conserved interactions with human mRNAs. The miRNA Regulatory Mechanisms section explains that repression of target mRNAs occurs through mRNA decay and reduced translation, supporting both mechanisms in the claim. (LLM, conf=0.94)
- Supportedcites Kim, Chang, & Baek, 2017 source
The Abstract says miRNAs recognize and downregulate target mRNAs. The CANONICAL SITE TYPES section identifies mRNA destabilization and translational repression as mechanisms of gene-expression downregulation, while noting that destabilization is the main mechanism. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, for majority of miRNAs, both strands have precisely defined 5′ termini, compared to their 3′ ends, suggesting evolutionary pressure to maintain the target‐determining sequence of both strands (Okamura et al., 2008; Ruby, Jan, et al., 2007; Ruby, Stark, et al., 2007; Seitz, Ghildiyal, & Zamore, 2008).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
What the sources say
- Not checked — no full text of the sourcecites Okamura et al., 2008 source
- Partly supportedcites Ruby, Jan, et al., 2007 sourceExperimental — accuracy not yet measured
The mir-1003 sequencing passage (Abstract; page not provided) says that each of two complementary small-RNA sets had a more consistent 5′ than 3′ terminus. The paper also identifies the 5′ seed as important for targeting and notes conservation of two mirtronic miRNA seeds (Abstract; page not provided). It does not establish this pattern for a majority of miRNAs or attribute it to evolutionary pressure to preserve the target-determining sequences of both strands. (LLM, conf=0.84)
- Partly supportedcites Seitz, Ghildiyal, & Zamore, 2008 sourceExperimental — accuracy not yet measured
The Results and Discussion report that, in flies, the 5′ ends of both miRNA and miRNA∗ strands are typically more precisely defined than their 3′ ends. The paper presents evolutionary pressure to preserve seed sequences as one possible explanation, alongside constraints on Argonaute loading. It does not establish the unqualified claim for miRNAs generally. (LLM, conf=0.83)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additional pairing between nucleotides in the 3′ half of the miRNA and the target mRNA also contribute to miRNA‐mediated gene targeting (reviewed in Chipman & Pasquinelli, 2019).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Chipman & Pasquinelli, 2019 source
In “Target recognition and regulation by miRNAs,” the review says that, after seed binding, nucleotides in the miRNA’s 3′ half can bind the target site and that 3′-end pairing can affect targeting specificity. “Same seed, different targets” also describes additional 3′-portion pairing as contributing to target interactions. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Selectively blocking the phosphorylation of the 5′ end of the guide strand in vitro leads to the loading of the passenger strand, consistent with either strand having the capacity to be loaded into miRISC (Kawamata et al., 2011).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Kawamata et al., 2011 source
In “RISC loading requires 5′ phosphate of the guide” (Fig. 1C–D; page not provided), the authors report that blocking the original guide strand’s 5′ end while phosphorylating the passenger strand led to Ago1-RISC formation with the passenger strand acting as guide. This supports the claim that either strand can be loaded as the guide under the tested conditions, provided it has a 5′ phosphate. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Consistently, the most commonly observed 5′ nucleotide of miRNA guide strands is a Uracil, whereas the passenger strand often begins with a Cytosine at the 5′ end (Ghildiyal et al., 2009; Mi et al., 2008; Takeda, Iwasaki, Watanabe, Utsumi, & Watanabe, 2008; Warf, Johnson, & Bass, 2011; Figure 2c).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Ghildiyal et al., 2009 source
In the section on miRNA/miRNA* duplex structure and Argonaute loading, the paper reports that 72% of miRNAs detected in fly heads began with U. It also reports that C was the most frequent first nucleotide of miRNA* (passenger) strands, at 32.1%. (LLM, conf=0.91)
- Not matchedcites Mi et al., 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Takeda et al., 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The first four nucleotides of each end of the duplex are believed to establish thermodynamic asymmetry, and the difference of a single extra hydrogen bond is sufficient to drive preferential loading of the less stable strand in vitro (Khvorova, Reynolds, & Jayasena, 2003; Krol et al., 2004; Schwarz et al., 2003).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Khvorova, Reynolds, & Jayasena, 2003 sourceExperimental — accuracy not yet measured
The Results and Discussion (page unavailable) analyze terminal-four-base stability and say that lower stability at a strand’s 5′ end favors its retention by RISC. The paper also reports in vitro findings on the relative stability of the two ends, citing Schwarz et al. (2003). Our copy does not say that a single extra hydrogen bond is sufficient to drive preferential loading in vitro. (LLM, conf=0.87)
- Partly supportedcites Krol et al., 2004 sourceExperimental — accuracy not yet measured
The “Thermodynamic Features of miRNA Precursors” section compares stability at the two duplex ends, including their terminal four nucleotides, but finds that the terminal two nucleotides distinguish miRNA from miRNA* most effectively. It does not report that one extra hydrogen bond suffices to drive preferential loading in vitro. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Supportedcites Schwarz et al., 2003 source
The Supplementary data (Figure S1 caption; page unavailable) identifies the relative stability of the first four base pairs at each strand’s 5′ end as explaining functional asymmetry. The Results and Discussion (page unavailable) report that a single-hydrogen-bond difference measurably affects RISC assembly and that the less stably paired strand is favored; the supplementary experiments describe in vitro RNAi reactions. (LLM, conf=0.91)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, in some closely‐related species, the preferred miRNA arm for homologous miRNA genes is not the same (de Wit et al., 2009; Griffiths‐Jones et al., 2011; Marco et al., 2010), consistent with the idea that, in at least some cases, miRNA arm switching could be evolutionarily favored.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites de Wit et al., 2009 source
The miRNA evolution mechanisms section reports that mir-246 has a dominant 3′ arm in C. elegans and C. briggsae but a dominant 5′ arm in C. remanei. The Figure 3 caption identifies this difference between related species as an example of arm switching. The suggestion that switching could be evolutionarily favored is the citing authors’ interpretation of that observation. (LLM, conf=0.91)
- Supportedcites Griffiths-Jones et al., 2011 source
In Results and Discussion, under “Arm choice has evolved in the miR-100/10 family” (page unavailable), the paper reports opposite dominant-arm usage for orthologous miR-10 in D. melanogaster and T. castaneum. It also describes arm switching as a way to change miRNA targets and function during evolution. The sentence’s suggestion that switching could be evolutionarily favored is a cautious interpretation of that finding, not a claim that this paper demonstrated selection for it. (LLM, conf=0.91)
- Partly supportedcites Marco et al., 2010 sourceExperimental — accuracy not yet measured
The Results (Functional Shifts in Insect miRNAs; page unavailable) report different dominant arms for homologous miRNAs in Drosophila and Tribolium, and the Discussion calls arm switching a source of evolutionary novelty. But the Discussion says these species’ conserved miRNAs span approximately 350 million years, so this example does not establish the claim about closely related species. The paper also does not show that switching was evolutionarily favored rather than simply observed. (LLM, conf=0.85)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, miRNA guide‐strand selection appears to occur independently of R2D2 as miRNA guide strand loading is not perturbed by loss of R2D2 function (Nishida et al., 2013; Okamura, Robine, Liu, Liu, & Lai, 2010).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Nishida et al., 2013 sourceExperimental — accuracy not yet measured
The Results report that miR-bantam’s distribution between Ago1 and Ago2 was hardly affected by R2D2 loss, and the Discussion says Ago1-associated miRNA levels were hardly changed. These findings support largely unchanged miRNA loading, but the paper’s explicit guide-versus-passenger strand-selection result concerns siRNAs, not miRNAs; it does not directly establish R2D2-independent miRNA guide-strand selection. (LLM, conf=0.85)
- Supportedcites Okamura, Robine, Liu, Liu, & Lai, 2010 source
The Results report that mature miRNA abundance was largely unchanged in AGO1 complexes from RNAi-defective mutants. The Discussion adds that AGO1 continued to preferentially incorporate mature miRNA strands when the RNAi pathway was disrupted, supporting the claim about guide-strand selection and loading despite loss of R2D2. (LLM, conf=0.90)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“It has been suggested that the ratio of miR::miR* strands may be influenced by target availability, as the presence of suitable mRNA targets can stabilize cognate miRNAs (Chatterjee, Fasler, Büssing, & Großhans, 2011; Tsai et al., 2016).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Chatterjee, Fasler, Büssing, & Großhans, 2011 source
The Introduction states that expressing miRNA targets increases cognate miRNA levels in C. elegans and that target availability may alter miR:miR∗ ratios. The Summary also reports that cognate target mRNAs protect miRNAs from degradation and can promote accumulation of certain miR∗ strands. (LLM, conf=0.94)
- Supportedcites Tsai et al., 2016 source
The Results section reports that adding binding sites or target 3′UTRs increased the levels of the corresponding miR-193a strands, and attributes differences in their ratio to target-gene expression. The Discussion states that target mRNA abundance can stabilise miRNA* strands. Page numbers are not provided in our copy. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“miR‐155* (3p) targets the Hsp40‐family genes Dnaja2 and Dnajb1, whose down‐regulation appears to directly contribute to the disease pathogenesis (Mycko et al., 2015), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Mycko et al., 2015 source
The targeting results (Fig. 4C) show that miR-155-3p directly targets Dnaja2 and Dnajb1 and reduces their expression. The Discussion reports that these genes suppress EAE and identifies their transcripts as critical to autoimmune demyelination, supporting the hedged claim that their down-regulation contributes to pathogenesis. Page numbers are not available in the supplied copy. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“While often supported by in vivo observations, such as the observation that most miRNAs begin with a 5′ Uracil (Ghildiyal et al., 2009; Mi et al., 2008; Takeda et al., 2008; Warf et al., 2011), how well these rules hold up in a living organism throughout its lifespan is yet to be established.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Supportedcites Ghildiyal et al., 2009 source
The section on miRNA/miRNA* duplex structure and Argonaute loading reports that 72% of miRNAs expressed in fly heads began with U, supporting the observation for which this paper is cited. The sentence’s question about whether strand-selection rules hold throughout an organism’s lifespan is the citing authors’ framing, not a finding attributed to this source. (LLM, conf=0.93)
- Not matchedcites Mi et al., 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Takeda et al., 2008 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Complicating the matters of miRNA strand stability being dictated by cognate target presence, numerous groups have reported target‐directed miRNA degradation (TDMD), a mechanism for target dependent miRNA decay (reviewed in Wightman, Giono, Fededa, & de la Mata, 2018).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Wightman, Giono, Fededa, & de la Mata, 2018 source
The Introduction describes this paper as a review of findings on TDMD. The General Features of TDMD section defines TDMD as target RNAs triggering degradation of mature miRNAs and cites multiple studies reporting it, supporting both the mechanism and the claim that multiple groups have reported it. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Further, modifications to the 3′ overhangs can also directly affect TS and can influence strand selection (Bramsen et al., 2009; Bramsen & Kjems, 2013; Ui‐Tei et al., 2012).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Bramsen et al., 2009 sourceExperimental — accuracy not yet measured
The Results section ('Modified overhangs alter strand selection by RISC'; page unavailable) reports that 3′-overhang modifications can favour incorporation of the opposing strand. It does not establish that those modifications directly affect TS; the Discussion instead says the strand-selection effect occurs irrespective of the duplex’s thermodynamic asymmetry. (LLM, conf=0.84)
- Not matchedcites Bramsen & Kjems, 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Ui-Tei et al., 2012 sourceExperimental — accuracy not yet measured
The section on thermodynamic control by chemical modifications (page unavailable) says that modifications at the 3′ ends of the guide and passenger strands alter duplex stability and can improve selective guide-strand loading. The paper identifies siRNAs as having 3′ overhangs, but it does not establish that the reported stability changes come specifically from modifying those overhangs rather than other 3′-end nucleotides. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Here, miR‐24‐2* (5p) directly targets PKCα (protein kinase C), a factor that is required for the survival of MCF‐7 breast cancer cells (Martin et al., 2012; Weldon et al., 2005).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Martin et al., 2012 source
The Results section reports that miR-24-2* represses PKCα mRNA and its 3′ UTR in MCF-7 cells. The Discussion describes this as direct inhibition and states that PKCα is critical for MCF-7 cell survival. Page numbers are not provided in our copy. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites Weldon et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“suggesting that regulation of TUT4/TUT7 activity can dictate strand selection of miR‐324 in humans, resulting in arm switching across tissues (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Kim et al., 2020 sourceExperimental — accuracy not yet measured
The section ‘miR-324 arm switching is controlled by TUT4 and TUT7’ reports that TUT4/7 knockdown changes the miR-324 strand ratio in human HEK293T cells. It also links TUT4/7 levels to strand ratios across mouse tissues, but the cited passages do not establish arm switching across human tissues specifically. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similar observations have been reported in flies, where several miRNA duplexes were found to exhibit tissue‐specific differences in miRNA strand selection (Ghildiyal et al., 2009).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites Ghildiyal et al., 2009 source
The Discussion reports different miRNA/miRNA* ratios for several duplexes in fly heads and ovaries, including a reversal of which strand is more abundant for miR-92a. This supports the cited observation of tissue-specific differences in strand selection; the paper presents the cause of those differences as a possibility, not a finding. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The abundance of miR‐193a‐5p, but not miR‐193‐3p is significantly decreased in breast cancer and is believed to be due to reduced availability of miR‐193a‐5p targets (Tsai et al., 2016).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Partly supportedcites Tsai et al., 2016 sourceExperimental — accuracy not yet measured
The Results section (‘Different arm expression preferences of miR-193a in breast cancer’; page unavailable) reports significantly lower miR-193a-5p in breast cancer tissue, with no difference in miR-193a-3p. The Discussion proposes that target-gene abundance may explain the differing arm levels, but does not establish that miR-193a-5p targets become less available in breast cancer; it specifically suggests that greater stabilization of miR-193a-3p may explain why that arm did not decline. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, miRNA arm switching has been proposed to influence miRNA evolution, as altered selection of a miRNA strand by Argonaute would be expected to result in a different mRNA target repertoire (de Wit, Linsen, Cuppen, & Berezikov, 2009; Griffiths‐Jones, Hui, Marco, & Ronshaugen, 2011; Marco, Hui, Ronshaugen, & Griffiths‐Jones, 2010).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Supportedcites de Wit, Linsen, Cuppen, & Berezikov, 2009 source
The Discussion proposes arm switching as a mechanism of miRNA evolution. The paper also explains that either hairpin arm can supply the miRNA loaded into RISC and that the mature miRNA’s seed determines target recognition. Together, these passages support the proposed change in target repertoire when the selected arm changes; the paper uses “RISC” rather than naming Argonaute in these passages. No page numbers are available in our copy. (LLM, conf=0.88)
- Supportedcites Griffiths-Jones, Hui, Marco, & Ronshaugen, 2011 source
The Introduction says that miRNAs from opposite arms can be sorted into different Argonaute complexes and that changes in arm usage may alter miRNA function. In Results and Discussion (‘Arm switching impacts mRNA target regulation’), the paper reports that targets predicted for the two arms do not overlap more than expected by chance. The supplied passages do not give page numbers. (LLM, conf=0.90)
- Supportedcites Marco, Hui, Ronshaugen, & Griffiths-Jones, 2010 source
The Results section reports that shifts in use of the 5′ and 3′ arms are predicted to change a miRNA’s target profile because the two arms produce different mature sequences. The Discussion identifies arm switching as a source of evolutionary novelty. The paper describes strand association with the RNA-induced silencing complex, though it does not name Argonaute in these passages. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As ethanol exposure promotes changes in the 5p/3p ratios of certain miRNAs, it is possible that de‐regulation of miRNA strand selection could play some role in alcohol abuse disorders (Ghezzi et al., 2016).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Partly supportedcites Ghezzi et al., 2016 sourceExperimental — accuracy not yet measured
The Discussion reports ethanol-related changes in the abundance of four miRNA passenger strands in Drosophila and suggests that those strands may have regulatory potential. It does not establish changes in 5p/3p ratios or propose that disrupted strand selection plays a role in alcohol abuse disorders. (LLM, conf=0.81)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Under TDMD, the presence of a target mRNA promotes cognate miRNA degradation, often with specific target mRNAs responsible for controlling miRNA decay (Ameres et al., 2010; Cazalla, Yario, Steitz, & Steitz, 2010; de la Mata et al., 2015; Ghini et al., 2018; Kleaveland, Shi, Stefano, & Bartel, 2018).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Ameres et al., 2010 sourceExperimental — accuracy not yet measured
The “miRNA sensors affect steady-state miRNA levels” section (page not provided) reports that engineered egfp mRNAs with complementary sites reduced the abundance of their corresponding miRNAs. This supports target-dependent, cognate miRNA loss, but does not establish that specific target mRNAs often control miRNA decay generally; the paper’s “Sequence requirements for miRNA remodeling” section says canonical animal miRNA-binding sites did not alter miRNA stability. (LLM, conf=0.84)
- Partly supportedcites Cazalla, Yario, Steitz, & Steitz, 2010 sourceExperimental — accuracy not yet measured
The supplied Abstract passage reports that the viral noncoding RNA HSUR 1 directs degradation of mature miR-27 through sequence-specific binding. This supports target-RNA-directed miRNA decay, but the identified RNA is not an mRNA, and the paper does not establish that specific target mRNAs often control miRNA decay. No page numbers are supplied for the passages. (LLM, conf=0.87)
- Supportedcites de la Mata et al., 2015 source
The Introduction defines TDMD as decay of miRNAs triggered by highly complementary target RNAs, including mRNAs. The Discussion reports that expression of highly complementary target mRNAs induces potent, specific miRNA degradation in neurons. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“miR‐574* (5p) targets QKI6 (Quaking), while miR‐574‐3p targets ACVR1B (activin receptor type‐1), and depleting one miRNA strand's target phenocopies the loss of the other miRNA strand in gastric cancer cells (Zhang et al., 2019).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Partly supportedcites Zhang et al., 2019 sourceExperimental — accuracy not yet measured
The Results section, “miR-574-5p/3p target endogenous QKI6 and ACVR1B, respectively” (page unavailable), identifies QKI6 and ACVR1B as direct targets of miR-574-5p and miR-574-3p, respectively. It reports that restoring target expression partly rescues the effects of the corresponding miRNA, but does not show that depleting one strand’s target phenocopies loss of the other strand. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“alters the sequence of miR‐146a* (3p) strand, and likely leads to changes in target repression, contributing to PTC (Jazdzewski et al., 2009; Labbaye & Testa, 2012), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not checked yetcites Jazdzewski et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
- Supportedcites Labbaye & Testa, 2012 source
The “miR-146a and cancer” section (page not provided) says the G/C polymorphism produces two passenger-strand isoforms, miR-146a*G and miR-146a*C, with distinct target genes. It also links the resulting changes in gene expression in heterozygotes to predisposition to papillary thyroid cancer. (LLM, conf=0.90)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, over one‐third of the genes regulated by miR‐574‐3p and miR‐574‐5p overlap, highlighting that although each strand contains a unique seed sequence, there can be substantial shared targets of the two strands (Zhang et al., 2019).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Partly supportedcites Zhang et al., 2019 sourceExperimental — accuracy not yet measured
The Results section on QKI6 and ACVR1B (Fig. 3j; page unavailable) reports that approximately one-third of the genes regulated by miR-574-5p and miR-574-3p overlap. It does not establish that the proportion is over one-third, and it describes the common targets as arising through direct or indirect pathways. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In animal models of multiple sclerosis, miR‐155* (3p) is highly up‐regulated in T‐helper (Th) cells, and promotes Th17 cell differentiation (Mycko et al., 2015).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Mycko et al., 2015 source
The Discussion reports that miR-155-3p is highly upregulated in T-helper cells during EAE, an animal model of multiple sclerosis. The Results section, “miR-155-3p presence in CD4+ T cells promotes Th17 development,” reports that its upregulation promotes Th17 differentiation after T-cell receptor activation. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Both strands appear to target Cyclin‐D (CCND1), Ajuba LIM protein (AJUBA) and heart developmental protein with EGF like domains (HEG1) and knocking down those targets phenocopies restored miR‐193b levels (Choi et al., 2019).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Choi et al., 2019 source
The Results section on direct binding reports that both miR-193b strands inhibit CCND1, AJUBA, and HEG1 through interactions with their mRNAs’ 3′UTRs (Figure 4). The Results section on target-gene down-regulation reports that knocking down each gene reduced invasion, migration, and colony formation in lung cancer cells, consistent with the effects of miR-193b (Figure 5). (LLM, conf=0.93)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TUT4/TUT7 uridylate the 3′ end of miR‐324‐3p, which changes the site of Dicer processing to generate a shorter miR‐324 duplex that undergoes reversed strand selection, stabilizing the miR‐324‐3p strand instead of the typically more abundant miR‐324‐5p strand (Figure 4c; Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Kim et al., 2020 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In fly ovaries, the miR‐92a‐3p, miR‐988‐3p, and miR‐284‐5p strands are expressed at higher levels than their corresponding passenger strands, while the miR‐92a‐5p, miR‐988‐5p, and miR‐284‐3p strands are expressed in excess within fly heads (Ghildiyal et al., 2009).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Partly supportedcites Ghildiyal et al., 2009 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports the claimed ovary-versus-head abundance patterns for miR-92a, miR-988, and miR-284, comparing each annotated miRNA with its miRNA* strand. Our copy does not identify those strands by 3p or 5p designation, so it does not establish that the specifically named strands correspond to the reported comparisons. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Consistently, restoration of miR‐223 (3p) in BRCA1, BAP1‐deficient cancer cells is synthetic lethal, probably due to repression of NHEJ components (Srinivasan et al., 2019).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Srinivasan et al., 2019 source
The Discussion states that a single miR223-3p transfection induced synthetic lethality in BRCA1- and BAP1-deficient malignancies, likely by destroying the required alternative NHEJ components CtIP and Pso4. The Results also report cytotoxicity in the tested BRCA1- and BAP1-deficient cancer cells. Page numbers are not provided in our copy. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In another example, both miR‐193b (3p) and miR‐193b* (5p) are down regulated in lung cancer and restoring the levels of either strand suppresses malignant phenotypes including metastatic potential and cell proliferation (Choi et al., 2019), (Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Choi et al., 2019 source
The Results section reports that both strands are down-regulated in metastatic lung cancer cells. It also reports that restoring either strand reduces migration and invasion; Figure 2 describes colony-forming assays showing reduced proliferative potential. The paper’s evidence is particularly focused on metastatic lung cancer cells. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In another example, a single point mutation (U–C) that affects the relative TS of the human miR‐133a duplex results in altered 5p/3p ratios of miR‐133a and is associated with atrial fibrillation presumably through effects on mRNA targeting (Ohanian et al., 2013; Figure 6d).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Partly supportedcites Ohanian et al., 2013 sourceExperimental — accuracy not yet measured
The Abstract Results and Discussion report that the 79T>C MIR133A2 variant weakens predicted duplex thermostability and changes the miR-133a-5p/3p ratio. The Results identify the variant in one patient with atrial fibrillation, but the Discussion calls its relationship to AF “questionable”; effects on mRNA targets are predicted, not demonstrated in patient tissue. Thus the claimed association through mRNA targeting overstates the evidence. (LLM, conf=0.90)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Intriguingly, TUT‐4/7 are up‐regulated in glioblastoma and miR‐324 arm switching appears to correlate with a poor prognosis (Kim et al., 2020).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Supportedcites Kim et al., 2020 source
In “Alteration of the miR-324 strand ratio affects cell cycle progression” (Figure 6B–C and Figure S6C), the paper reports that both TUT4 and TUT7 are significantly upregulated in glioblastoma and that patients with low miR-324-5p/3p ratios had poor prognosis. This supports the citing sentence’s cautious description of an association between altered arm usage and prognosis. (LLM, conf=0.94)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“miR‐21* (3p) downregulation of PPACTR4 appears to decrease protein phosphatase 1 (PP1) activity leading to increased phosphorylation and inactivation of the tumor suppressor Rb/E2F (retinoblastoma/E2 transcription factor), ultimately resulting in tumorigenesis (Ge et al., 2015; Ohanian et al., 2013).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not matchedcites Ge et al., 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Could not verifycites Ohanian et al., 2013 sourceExperimental — accuracy not yet measured
The Results section on the MIR133A2 variant reports altered miR-133a-5p abundance, and the Discussion addresses predicted miR-133a targets. Searches for miR-21*, PPACTR4, PP1, Rb/E2F, and tumorigenesis found no passage in our copy addressing the claimed pathway. (LLM, conf=0.76)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Each miRNA is post‐transcriptionally processed into a duplex comprising two strands.”
§ microRNA strand selection: Unwinding the rules > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The Argonaute‐loaded miRNA programs the gene target specificity of the miRISC, as nucleotides 2‐7, referred to as the miRNA “seed” sequence, are mainly responsible for determining the target mRNA identity through base pairing (Grün, Wang, Langenberger, Gunsalus, & Rajewsky, 2005; Haley & Zamore, 2004; Jackson et al., 2003; Krek et al., 2005; Lewis, Burge, & Bartel, 2005; Lewis, Shih, Jones‐Rhoades”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
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In the paper
“The target gene specificity of miRISC is determined by sequence complementarity between the Argonaute‐loaded miRNA strand and target mRNA.”
§ microRNA strand selection: Unwinding the rules > Abstract
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In the paper
“Residues within the Argonaute PIWI domain contribute to a phosphate binding tract that is formed along the interface of the MID and PIWI domains that is proposed to sense TS while a nucleotide selection loop within the MID domain senses the identity of the 5′ nucleotide (Suzuki et al., 2015; Figure 2a).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Suzuki et al., 2015 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, miRNA strand selection plays a defining role in dictating the specificity of miRISC toward its targets and provides a mechanism to alter gene expression in a switch‐like fashion.”
§ microRNA strand selection: Unwinding the rules > Abstract
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In the paper
“Consistently, the 5′ ends of guide strands have been found to contain an excess of purines, whereas the 5′ ends of passenger strands are pyrimidine rich in humans and flies, which likely contributes to thermodynamic asymmetry between the two duplex ends (Hu et al., 2009).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not matchedcites Hu et al., 2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Not matched
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In the paper
“One strand of the miRNA duplex is selectively anchored into the Argonaute protein and determines the specificity of the miRISC based on sequence complementarity between the miRNA and the 3′UTR of the target mRNA (Figure 1, Step 5).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Each strand of the miRNA duplex has the capacity to be loaded into miRISC and possesses a unique seed sequence.”
§ microRNA strand selection: Unwinding the rules > Abstract
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The miRNA duplex is then loaded into an Argonaute protein to form the miRNA‐Induced Silencing Complex (miRISC; Figure 1, Step 5).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
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In the paper
“miRNAs that share a common seed sequence, referred to as miRNA families, can target the same group of mRNA substrates, at least in a partially redundant manner.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
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In the paper
“While either strand can be selected for miRISC loading, frequently, a single miRNA strand predominates.”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One of the two miRNA strands is selectively loaded into an Argonaute protein to form the miRNA‐Induced Silencing Complex (miRISC) in a process referred to as miRNA strand selection. The other strand is ejected from the complex and is subject to degradation.”
§ microRNA strand selection: Unwinding the rules > Abstract
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In the paper
“For most miRNAs, one strand is preferentially loaded into Argonaute and becomes part of the miRISC, originally earning the designation of the “miR” or “guide” strand. The other strand of the miRNA duplex is ejected from the Argonaute protein and degraded (Figure 1, Step 5′).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF microRNA BIOGENESIS AND FUNCTION
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In the paper
“Perhaps not surprisingly, Argonaute protein appears to play a direct role in miRNA strand selection, as recombinant Argonaute MID domain is sufficient to recognize the preferred 5′ nucleotide and to favor thermodynamically unstable ends (Suzuki et al., 2015).”
§ microRNA strand selection: Unwinding the rules > OVERVIEW OF miRISC LOADING AND miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Suzuki et al., 2015 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Aberrant strand selection can lead to altered gene regulation by miRISC and is observed in several human diseases including cancer.”
§ microRNA strand selection: Unwinding the rules > Abstract
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While sequestering miRNA arms might not affect the 5p/3p ratio of a given miRNA, it could alter the balance of target repression by each miRNA arm.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ability of cells to switch the miRNA arm preference is also evident from cases of physiological or pathogenic states, further supporting the idea that miRNA strand selection is a regulated process.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mechanisms influencing the production of isomiRs (highlighted in bold) have been experimentally demonstrated to influence 5p/3p ratios of miRNAs and can lead to miRNA arm switching, whereas other mechanisms remain largely hypothetical”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, isomiRs may be a dominant mechanism driving miRNA strand selection, or arm switching, although it remains possible that unidentified regulators play substantial roles.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“It is also possible that circRNAs, which have been proposed to act as miRNA sponges (reviewed in Kristensen et al., 2019; Thomson & Dinger, 2016), could influence miRNA arm availability by sequestering miRNAs that have target sites within the circRNA.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the presence of “decay targets” may in theory influence the 5p/3p ratios of certain miRNAs through TDMD.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We propose that strand selection is likely the dominant mechanism leading to altered arm ratios, as miRNA turnover would be expected to influence miRNA arm ratios after a dominant miRNA strand is selected.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While the 5′‐nucleotide preference and TS rules are considered to be the primary factors driving miRNA strand selection during Argonaute loading, strand selection of all miRNAs may not be explained by these two rules only.”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“While the nature of these modifications in miRNA strand selection have not been fully explored, such alterations could presumably influence the TS of all small RNA duplexes and subsequently affect strand selection.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“however, deletion of the PAZ domain did not alter miRNA loading, suggesting PAZ domain is not required for sensing TS (Suzuki et al., 2015).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not checked — no full text of the sourcecites Suzuki et al., 2015 source
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These isomiRs can contain truncations or additions to the miRNA duplex and can alter the 5′ nucleotide identity of either, or both, strands.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: miRNA processing by Drosha or Dicer at alternate cut sites results in isomiRs that match the genomically encoded pre-miRNA sequence and are referred to as templated isomiRs.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional accessory factors may also play a role in miRNA strand selection, most likely through isomiR formation.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In human cells, DNA damage has been shown to promote changes in the expression of miRNAs (Dickey, Zemp, Martin, & Kovalchuk, 2011)”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not checked — no full text of the sourcecites Dickey, Zemp, Martin, & Kovalchuk, 2011 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, several mechanisms may contribute to altered miRNA 5p/3p ratios with regulation of miRNA strand selection likely playing a dominant role (Figure 5).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, miRBase‐annotated miRNA sequences or abundances may not be able to accurately reflect tissue‐dependent expression of miRNAs, making it difficult to define a single miRNA duplex from which any given miRNA strand originates.”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
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In the paper
“Notably, the miR‐194‐3p strand was nearly undetectable in brain and stomach tissues but was expressed at least as strongly as the miR‐194‐5p strand in other tissues including lungs, ovaries and uteri (Ro et al., 2007).”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
What the sources say
- Not matchedcites Ro et al., 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“While the miRNA guide strand is usually observed in extreme excess to its corresponding passenger strand, growing evidence supports that the relative levels of the two strands are highly regulated.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Overexpression of miR‐574 *(5p) enhances cell proliferation while expression of miR‐574 (3p) suppresses proliferation.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While data suggest that Argonaute proteins contribute to miRNA strand selection by recognizing both the 5′ nucleotide and relative TS of miRNA strands, it has become increasingly clear that these rules can be “circumvented” under different physiological or pathological conditions, primarily through duplex sequence alterations or isomiR production.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both miRNA strands can be functional, with arm switching playing a role during development through tissue‐specific or perhaps temporally‐regulated miRNA strand selection.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, multiple mechanisms may be involved in regulation of miRNA strand selection, with combinations of molecular inputs dictating which miRNA becomes loaded and to what extent.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the rules governing miRNA strand selection were determined using a limited number of purified components; whether these rules are sufficient to drive strand selection in vivo has not been extensively explored.”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, altered miRNA strand selection is associated with disease, presumably due to targeting distinct sets of mRNAs (Figure 7).”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“In squamous cell carcinoma, both miR‐21 (5p) and miR‐21* (3p) are up‐regulated and each is required for cell survival (Ge et al., 2015; Figure 6c, Table 1).”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
What the sources say
- Not matchedcites Ge et al., 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these data highlight that miRNA strand selection can be highly regulated and alterations to this normally robust process can have dramatic consequences and are prevalent in human disease.”
§ microRNA strand selection: Unwinding the rules > ALTERNATIVE miRNA STRAND USAGE IN HUMAN DISEASE
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are at least three known regulatory points for miRNA strand selection: (a) altered processing of the miRNAs by RNAse III endonucleases generating templated isomiRs, (b) nontemplated miRNA isomiRs generated through deamination (A‐I editing) or uridylation, which remodel the miRNA duplex, and (c) altered strand preference of Argonaute (Figure 7).”
§ microRNA strand selection: Unwinding the rules > SUMMARY AND PERSPECTIVES
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The authors state this as an assumption.
The most abundant 5p and 3p miRNA strands originate from the same duplex.
“However, this analysis carries an assumption that the most abundant 5p and 3p miRNA strands originate from the same duplex (Figure 3d).”
The paper relies on this without support.
The same miRNA precursor can produce distinct miRNA isoforms, collectively known as isomiRs.
“The same miRNA precursor can produce distinct miRNA isoforms, collectively known as isomiRs.”
The paper relies on this without support.
miRNA processing by Drosha or Dicer at alternate cut sites results in isomiRs that match the genomically encoded pre-miRNA sequence and are referred to as templated isomiRs.
“miRNA processing by Drosha or Dicer at alternate cut sites results in isomiRs that match the genomically‐encoded pre‐miRNA sequence and are referred to as “templated isomiRs” (Figure 4a,b).”
The paper relies on this without support.
Most miRNA duplexes contain two nucleotide overhangs at their 3′ ends.
“Furthermore, most miRNA duplexes contain two nucleotide overhangs at their 3′ ends.”
The paper relies on this without support.
Under wild-type conditions, most miRNAs have a dominantly expressed miRNA strand.
“While under wild‐type conditions, most miRNAs have a dominantly expressed miRNA strand (Figure 6a)”
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The cited source says what the claim attributes to it.
In the citing paper
“Both arms of the miRNAs can be expressed as a mature form in vivo (17, 18).”
From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
“We considered that a miRNA duplex did not follow the TS rule if the duplex end correlating with the dominant strand's 5′ end had a higher or equal free energy than the duplex end producing the passenger strand.”
§ microRNA strand selection: Unwinding the rules > HOW WELL DO miRNAs FOLLOW THE RULES?
“miRNAs with equal or higher thermodynamic stability on the guide end of the duplex compared to the passenger end of the duplex were not considered to follow the thermodynamic stability rule.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
“In wild‐type tissues expressing low levels of terminal 3′ uridylases (TUTases), nonuridylated miR‐324‐5p is selected for miRISC loading. In Glioblastoma, high expression of TUTases leads to uridylation of miR‐324‐3p, altered Dicer specificity and reversed strand selection toward miR‐324‐5p.”
§ microRNA strand selection: Unwinding the rules > REGULATION OF miRNA STRAND SELECTION
“TUT4/TUT7 uridylate the 3′ end of miR‐324‐3p, which changes the site of Dicer processing to generate a shorter miR‐324 duplex that undergoes reversed strand selection, stabilizing the miR‐324‐3p strand instead of the typically more abundant miR‐324‐5p strand”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“Xu, J.‐H., Chen, R.‐Z., Liu, L.‐Y., Li, X.‐M., Wu, C.‐P., Zhou, Y.‐T., … Zhang, Z.‐Y. (2020). LncRNA ZEB2‐AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR‐574‐3p/HMGA2 axis. European Review for Medical and Pharmacological Sciences, 24(10), 5391– 5403. 10.26355/eurrev_202005_21323 32495874”
Cited work 10.26355/eurrev_202005_21323 · retraction date not known · this paper published 2020-09-20
Citations
Cites
1 retracted
Xu, J., Chen, R.-Z., Liu, L.-Y., Li, X. M., Wu, C., Zhou, Y.-T., Yan, J.-D., & Zhang, Z.-Y. (2020) · PubMed · doi:10.26355/eurrev_202005_21323 · Cited by 10
RetractedLewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855
The nuclear RNase III Drosha initiates microRNA processing
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Rådmark, O., Kim, S., et al. (2003) · Nature · doi:10.1038/nature01957 · Cited by 5,299
Prediction of Mammalian MicroRNA Targets
Lewis, B. P., Shih, I.-H., Jones-Rhoades, M. W., Bartel, D. P., & Burge, C. B. (2003) · Cell · doi:10.1016/s0092-8674(03)01018-3 · Cited by 5,199
Lorenz, R., Bernhart, S. H., Höner zu Siederdissen, C., Tafer, H., Flamm, C., Stadler, P. F., & Hofacker, I. L. (2011) · Algorithms for Molecular Biology · doi:10.1186/1748-7188-6-26 · Cited by 5,098
miRBase: from microRNA sequences to function
Kozomara, A., Birgaoanu, M., & Griffiths-Jones, S. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1141 · Cited by 4,843
The biogenesis, biology and characterization of circular RNAs
Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0158-7 · Cited by 4,823
Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
Lim, L. P., Lau, N. C., Garrett-Engele, P., Grimson, A., Schelter, J. M., Castle, J., Bartel, D. P., Linsley, P. S., & Johnson, J. M. (2005) · Nature · doi:10.1038/nature03315 · Cited by 4,755
Combinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
MicroRNA genes are transcribed by RNA polymerase II
Lee, Y., Kim, M., Han, J., Yeom, K.-H., Lee, S., Baek, S. H., & Kim, V. N. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600385 · Cited by 4,556
Research works printed but not linked: 1
- Ma D. L., 2016, Influence of continuous intervention on growth and metastasis of human cervical cancer cells and expression of RNAmiR‐574‐5p, Journal of Biological Regulators and Homeostatic Agents, 30, 91
Cited by
Sorted by citations
RNA-based therapeutics: an overview and prospectus
Zhu, Y., Zhu, L., Wang, X., & Jin, H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05075-2 · Cited by 683
Metcalf, G. (2024) · Oncogene · doi:10.1038/s41388-024-03076-3 · Cited by 218
Recent progress in miRNA biogenesis and decay
Ros, X. B., & Ørom, U. A. (2023) · RNA Biology · doi:10.1080/15476286.2023.2288741 · Cited by 118
Kuo, M., Liu, S. C.-H., Hsu, Y.-F., & Wu, R. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00775-x · Cited by 99
The Role of microRNA in the Inflammatory Response of Wound Healing
Jiang, Y., Xu, X. Z., Xiao, L., Wang, L., & Qiang, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.852419 · Cited by 97
Metadata
- Authors
- Medley, J. C., Panzade, G., & Zinovyeva, A. Y.
- Affiliations
- Kansas State University (US)
- Corresponding author
- Zinovyeva, Anna Y.
- Venue
- WIREs RNA
- Publisher
- Wiley
- Published
- 2020-09-20
- Volume
- 12
- Issue
- 3
- Pages
- e1627-e1627
- ISSN
- 1757-7004 (ISSN-L)
- 1757-7012
- PMC
- PMC8047885
- OpenAlex
- W3087056556
- Cited by
- 225
- References
- 200
- Citations by year
- 2026: 31 · 2025: 52 · 2024: 53 · 2023: 36 · 2022: 33 · 2021: 18 · 2020: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Wiley Interdisciplinary Reviews - RNA (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R35GM124828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- Argonaute proteins, miRNA-induced silencing complex, seed sequence, post-transcriptional regulation, microRNA biogenesis, target specificity, cancer, small regulatory RNAs
- MeSH terms
- Humans, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA Interference, MicroRNAs, Argonaute Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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