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Cited by 225MicroRNA in disease regulationRNA Interference and Gene DeliveryPlant Molecular Biology Research

microRNA strand selection: Unwinding the rules

Open access
Medley, Jeffrey C., Panzade, Ganesh, Zinovyeva, Anna Y.·2021·WIREs RNA
DOI 10.1002/wrna.1627PMC PMC8047885
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Abstract

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

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.

Integrity signals

Registry

Crossref · 10.1002/wrna.1627

Cites

200 of 200 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

1 of 139 cited sources checked · 1 supported · 0 flagged

  • Findingown data

    17-25% of miRNA duplexes did not follow either the 5' nt preference or TS rules.

    “Strikingly, 17–25% of miRNA duplexes did not follow either the 5′ nt preference or TS rules (Figures 3a–c).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The most abundant 5p and 3p miRNA strands originate from the same duplex.
  • Findingown data

    In each organism examined (C. elegans, Drosophila, and humans), half of all miRNAs did not follow one of the two rules for miRNA strand selection.

    “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).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The most abundant 5p and 3p miRNA strands originate from the same duplex.
  • Findingown data

    A significant number of miRNAs do not follow either the 5′ nucleotide or TS rules.

    “At first glance, a significant number of miRNAs do not follow either the 5′ nucleotide or TS rules (see Figure 3).”
    Quote in the paperSubstantial claim
  • Premisecitation

    Argonaute appears to favor loading the end of the duplex that contains the lower relative thermodynamic stability.

    “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.”
    Quote in the paperNot a substantial claim
  • Interpretationreasoning

    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.

    “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).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 28
  • May combine two claims. 58

  • Classified as probably not a substantial claim.

    Premisecitation

    microRNAs (miRNAs) regulate gene expression by targeting specific mRNAs for degradation or translational repression.

    “microRNAs (miRNAs) play a central role in the regulation of gene expression by targeting specific mRNAs for degradation or translational repression.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Bartel, 2018 source
    • cites Kim, Chang, & Baek, 2017 source

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Each miRNA is post-transcriptionally processed into a duplex comprising two strands.

    “Each miRNA is post‐transcriptionally processed into a duplex comprising two strands.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Less abundant miR* strands were shown to repress mRNAs containing predicted miR* target sites in flies and mammals, suggesting that miR* strands are functional.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Okamura et al., 2008 source
    • cites Yang et al., 2010 source

  • May combine two claims.

    Premisecitation

    The Argonaute-loaded miRNA programs the gene target specificity of miRISC, as nucleotides 2-7 (the seed sequence) are mainly responsible for determining target mRNA identity through base pairing.

    “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”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Grün et al., 2005

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Haley & Zamore, 2004 source
    • cites Jackson et al., 2003 source

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The target gene specificity of miRISC is determined by sequence complementarity between the Argonaute-loaded miRNA strand and target mRNA.

    “The target gene specificity of miRISC is determined by sequence complementarity between the Argonaute‐loaded miRNA strand and target mRNA.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Residues within the Argonaute PIWI domain contribute to a phosphate binding tract along the MID/PIWI interface that is proposed to sense thermodynamic stability, while a nucleotide selection loop within the MID domain senses the identity of the 5' nucleotide.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Suzuki et al., 2015 source

  • May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hu et al., 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    ALG-1 mutations that affect strand selection 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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zinovyeva et al., 2015 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    One strand of the miRNA duplex is selectively anchored into Argonaute and determines the specificity of miRISC based on sequence complementarity between the miRNA and the 3'UTR of the target mRNA.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    For the 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.

    “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).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Okamura et al., 2008 source
    • cites Ruby, Jan, et al., 2007 source
    • cites Seitz, Ghildiyal, & Zamore, 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Additional pairing between nucleotides in the 3' half of the miRNA and the target mRNA also contributes to miRNA-mediated gene targeting.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chipman & Pasquinelli, 2019 source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Each strand of the miRNA duplex has the capacity to be loaded into miRISC and possesses a unique seed sequence.

    “Each strand of the miRNA duplex has the capacity to be loaded into miRISC and possesses a unique seed sequence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kawamata et al., 2011 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The miRNA duplex is loaded into an Argonaute protein to form miRISC.

    “The miRNA duplex is then loaded into an Argonaute protein to form the miRNA‐Induced Silencing Complex (miRISC; Figure 1, Step 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The most commonly observed 5' nucleotide of miRNA guide strands is Uracil, whereas the passenger strand often begins with Cytosine at the 5' end.

    “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).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Ghildiyal et al., 2009 source
    • cites Mi et al., 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Takeda et al., 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    miRNAs that share a common seed sequence can target the same group of mRNA substrates, at least in a partially redundant manner.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    While either strand can be selected for miRISC loading, frequently a single miRNA strand predominates.

    “While either strand can be selected for miRISC loading, frequently, a single miRNA strand predominates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    One of the two miRNA strands is selectively loaded into an Argonaute protein to form miRISC, and the other strand is ejected from the complex and degraded.

    “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.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    For most miRNAs, one strand is preferentially loaded into Argonaute and becomes the guide strand, while the other strand is ejected and degraded.

    “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′).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Suzuki et al., 2015 source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Aberrant strand selection can lead to altered gene regulation by miRISC and is observed in several human diseases including cancer.

    “Aberrant strand selection can lead to altered gene regulation by miRISC and is observed in several human diseases including cancer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Khvorova, Reynolds, & Jayasena, 2003 source
    • cites Krol et al., 2004 source
    • cites Schwarz et al., 2003 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The ability of cells to switch miRNA arm preference is evident from cases of physiological or pathogenic states, further supporting the idea that miRNA strand selection is a regulated process.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In some closely-related species, the preferred miRNA arm for homologous miRNA genes is not the same, consistent with the idea that, in at least some cases, miRNA arm switching could be evolutionarily favored.

    “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.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites de Wit et al., 2009 source
    • cites Griffiths-Jones et al., 2011 source
    • cites Marco et al., 2010 source

  • May combine two claims.

    Interpretationnone given

    Mechanisms influencing the production of isomiRs have been experimentally demonstrated to influence 5p/3p ratios of miRNAs and can lead to miRNA arm switching, whereas other mechanisms remain largely hypothetical.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    miRNA guide-strand selection appears to occur independently of R2D2 as miRNA guide strand loading is not perturbed by loss of R2D2 function.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Nishida et al., 2013 source
    • cites Okamura, Robine, Liu, Liu, & Lai, 2010 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The ratio of miR::miR* strands may be influenced by target availability, as the presence of suitable mRNA targets can stabilize cognate miRNAs.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Chatterjee, Fasler, Büssing, & Großhans, 2011 source
    • cites Tsai et al., 2016 source

  • May combine two claims.

    Premisecitation

    miR-155* (3p) targets Hsp40-family genes Dnaja2 and Dnajb1, whose down-regulation appears to directly contribute to disease pathogenesis.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mycko et al., 2015 source

  • May combine two claims.

    Interpretationreasoning

    IsomiRs may be a dominant mechanism driving miRNA strand selection, or arm switching, although it remains possible that unidentified regulators play substantial roles.

    “Overall, isomiRs may be a dominant mechanism driving miRNA strand selection, or arm switching, although it remains possible that unidentified regulators play substantial roles.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    While often supported by in vivo observations, how well the rules of miRNA strand selection hold up in a living organism throughout its lifespan is yet to be established.

    “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.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Ghildiyal et al., 2009 source
    • cites Mi et al., 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Takeda et al., 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    circRNAs, which have been proposed to act as miRNA sponges, could influence miRNA arm availability by sequestering miRNAs that have target sites within the circRNA.

    “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.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kristensen et al., 2019 source
    • cites Thomson & Dinger, 2016 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Numerous groups have reported target-directed miRNA degradation (TDMD), a mechanism for target dependent miRNA decay.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wightman, Giono, Fededa, & de la Mata, 2018 source

  • May combine two claims.

    Premisecitation

    Modifications to the 3' overhangs can directly affect TS and can influence strand selection.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bramsen et al., 2009 source
    • cites Bramsen & Kjems, 2013

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Ui-Tei et al., 2012 source

  • May combine two claims.

    Premisecitation

    miR-24-2* (5p) directly targets PKCα, a factor required for the survival of MCF-7 breast cancer cells.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Martin et al., 2012 source
    • cites Weldon et al., 2005 source

  • May combine two claims.

    Interpretationcitation

    Regulation of TUT4/TUT7 activity can dictate strand selection of miR-324 in humans, resulting in arm switching across tissues.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kim et al., 2020 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The presence of decay targets may in theory influence the 5p/3p ratios of certain miRNAs through TDMD.

    “Thus, the presence of “decay targets” may in theory influence the 5p/3p ratios of certain miRNAs through TDMD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Similar observations have been reported in flies, where several miRNA duplexes were found to exhibit tissue-specific differences in miRNA strand selection.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ghildiyal et al., 2009 source

  • May combine two claims.

    Interpretationnone given

    While the 5' nucleotide preference and TS rules are considered to be the primary factors driving miRNA strand selection, strand selection of all miRNAs may not be explained by these two rules only.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tsai et al., 2016 source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    While the nature of these modifications in miRNA strand selection has not been fully explored, such alterations could presumably influence the TS of all small RNA duplexes and subsequently affect strand selection.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Deletion of the PAZ domain did not alter miRNA loading, suggesting the PAZ domain is not required for sensing TS.

    “however, deletion of the PAZ domain did not alter miRNA loading, suggesting PAZ domain is not required for sensing TS (Suzuki et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Suzuki et al., 2015 source

  • May combine two claims.

    Interpretationreasoning

    Templated isomiRs can contain truncations or additions to the miRNA duplex and can alter the 5′ nucleotide identity of either or both strands.

    “These isomiRs can contain truncations or additions to the miRNA duplex and can alter the 5′ nucleotide identity of either, or both, strands.”
    Quote in the paperSubstantial claim
    • 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.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites de Wit, Linsen, Cuppen, & Berezikov, 2009 source
    • cites Griffiths-Jones, Hui, Marco, & Ronshaugen, 2011 source
    • cites Marco, Hui, Ronshaugen, & Griffiths-Jones, 2010 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    De-regulation of miRNA strand selection could play some role in alcohol abuse disorders.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ghezzi et al., 2016 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Additional accessory factors may also play a role in miRNA strand selection, most likely through isomiR formation.

    “Additional accessory factors may also play a role in miRNA strand selection, most likely through isomiR formation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    miR-574* (5p) is oncogenic in colorectal cancer, NSCLC, and PTC, while miR-574 (3p) is tumor suppressive in breast cancer and leukemia.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cui, Tang, Chen, & Wang, 2014 source
    • cites Ji et al., 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Ma et al., 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Under TDMD, the presence of a target mRNA promotes cognate miRNA degradation, often with specific target mRNAs responsible for controlling miRNA decay.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Ameres et al., 2010 source
    • cites Cazalla, Yario, Steitz, & Steitz, 2010 source
    • cites de la Mata et al., 2015 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In human cells, DNA damage promotes changes in the expression of miRNAs.

    “In human cells, DNA damage has been shown to promote changes in the expression of miRNAs (Dickey, Zemp, Martin, & Kovalchuk, 2011)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dickey, Zemp, Martin, & Kovalchuk, 2011 source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Several mechanisms may contribute to altered miRNA 5p/3p ratios with regulation of miRNA strand selection likely playing a dominant role.

    “Overall, several mechanisms may contribute to altered miRNA 5p/3p ratios with regulation of miRNA strand selection likely playing a dominant role (Figure 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ro et al., 2007

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    miR-574* (5p) targets QKI6 (Quaking), while miR-574-3p targets ACVR1B, and depleting one miRNA strand's target phenocopies the loss of the other miRNA strand in gastric cancer cells.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhang et al., 2019 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The G/C polymorphism alters the sequence of miR-146a* (3p) strand and likely leads to changes in target repression, contributing to PTC.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jazdzewski et al., 2009 source
    • cites Labbaye & Testa, 2012 source

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zhang et al., 2019 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In animal models of multiple sclerosis, miR-155* (3p) is highly up-regulated in T-helper (Th) cells and promotes Th17 cell differentiation.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mycko et al., 2015 source

  • May combine two claims.

    Premisecitation

    Both miR-193b 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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Choi et al., 2019 source

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kim et al., 2020 source

  • May combine two claims.

    Premisecitation

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Overexpression of miR-574* (5p) enhances cell proliferation while expression of miR-574 (3p) suppresses proliferation.

    “Overexpression of miR‐574 *(5p) enhances cell proliferation while expression of miR‐574 (3p) suppresses proliferation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ghildiyal et al., 2009 source

  • May combine two claims.

    Premisecitation

    Restoration of miR-223 (3p) in BRCA1, BAP1-deficient cancer cells is synthetic lethal, probably due to repression of NHEJ components.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Srinivasan et al., 2019 source

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Choi et al., 2019 source

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ohanian et al., 2013 source

  • May combine two claims.

    Interpretationreasoning

    Argonaute proteins contribute to miRNA strand selection by recognizing both the 5′ nucleotide and relative TS of miRNA strands, but these rules can be circumvented under different physiological or pathological conditions, primarily through duplex sequence alterations or isomiR production.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Both miRNA strands can be functional, with arm switching playing a role during development through tissue-specific or perhaps temporally-regulated miRNA strand selection.

    “Both miRNA strands can be functional, with arm switching playing a role during development through tissue‐specific or perhaps temporally‐regulated miRNA strand selection.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Altered miRNA strand selection is associated with disease, presumably due to targeting distinct sets of mRNAs.

    “Similarly, altered miRNA strand selection is associated with disease, presumably due to targeting distinct sets of mRNAs (Figure 7).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In squamous cell carcinoma, both miR-21 (5p) and miR-21* (3p) are up-regulated and each is required for cell survival.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ge et al., 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    TUT-4/7 are up-regulated in glioblastoma and miR-324 arm switching appears to correlate with a poor prognosis.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kim et al., 2020 source

  • May combine two claims.

    Interpretationcitation

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    There are at least three known regulatory points for miRNA strand selection: altered processing by RNAse III endonucleases generating templated isomiRs, nontemplated miRNA isomiRs generated through deamination or uridylation, and altered strand preference of Argonaute.

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    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, ultimately resulting in tumorigenesis.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ge et al., 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Ohanian et al., 2013 source
76 of 76

  • 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)”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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.

  • Thermodynamic-stability rule uses opposite criteria in text and figure

    Minor

    The methods text classifies a guide end with higher free energy-and thus lower stability-as not following the rule. Figure 3 instead classifies a guide end with equal or higher stability as not following it; the paper also states that lower-stability ends are favored for loading.

  • Figure 4 reverses the stated direction of miR‐324 strand switching

    Minor

    The Figure 4 caption says wild-type tissue selects miR‐324‐5p and that uridylation reverses selection toward the same strand. The main text instead says uridylation stabilizes miR‐324‐3p rather than miR‐324‐5p.

2 of 2

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.

  • Cites a retracted work: 10.26355/eurrev_202005_21323

    Info

    The cited work was retracted; the date of the notice is not on record.

    Cited work 10.26355/eurrev_202005_21323 · retraction date not known · this paper published 2020-09-20

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  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

Related

Authors
Medley, J. C., Panzade, G., & Zinovyeva, A. Y.
Affiliations
Kansas State University (US)
Corresponding author
Zinovyeva, Anna Y.
ORCID
Venue
WIREs RNA
Publisher
Wiley
Published
2020-09-20
Volume
12
Issue
3
Pages
e1627-e1627
ISSN
  • 1757-7004 (ISSN-L)
  • 1757-7012
DOI
10.1002/wrna.1627
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
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

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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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-06.

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