A mouse tissue atlas of small noncoding RNA

In the paper

“a process previously thought to be strictly pathogenic in mammals (43, 45, 67).”

What the sources say

• Disputed

  The Introduction (page unavailable) describes arm switching across tissues and developmental stages, citing previous studies, and calls it a basic mechanism in miRNA evolution. The paper does not portray it as having been thought strictly pathogenic in mammals; it discusses cancer as one setting in which arm switching occurs. (LLM, conf=0.82)

  Checked by a reasoning model — may be wrong.

  cites [43] Chen L., miRNA arm switching identifies novel tumour biomarkers. EBioMedicine 38, 37– 46 (2018). 30425004 PMC6306400 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) says earlier studies described selective arm switches in multiple pathological conditions. It does not say arm switching was previously thought to be strictly pathogenic in mammals; it also discusses tissue-specific arm shifts and physiological conditions. The claim’s historical exclusivity is therefore unsupported. (LLM, conf=0.78)

  cites [45] Kern F., miRSwitch: Detecting microRNA arm shift and switch events. Nucleic Acids Res. 48, W268– W274 (2020). 32356893 PMC7319450 sourceExperimental — accuracy not yet measured
• Disputed

  The Introduction (page unavailable) says earlier studies reported changes in miRNA arm expression across tissues, developmental stages, and species, as well as during cancer progression. That account of prior research is contrary to the claim that arm switching was previously thought to be strictly pathogenic in mammals. (LLM, conf=0.74)

  Checked by a reasoning model — may be wrong.

  cites [67] Lin M., Comprehensive identification of microRNA arm selection preference in lung cancer: miR-324-5p and -3p serve oncogenic functions in lung cancer. Oncol. Lett. 15, 9818– 9826 (2018). 29844840 PMC5958786 sourceExperimental — accuracy not yet measured

In the paper

“Through their interactions with ribosomes and mRNA, these small noncoding molecules shape the dynamic molecular spectrum of tissues (4, 17).”

What the sources say

• Partly supported

  The Introduction (page unavailable) says a stress-produced tRNA fragment binds ribosomes and competes with mRNA, reducing protein synthesis. It also describes small RNAs as regulators of cellular RNomes, but the paper does not establish that these interactions shape the molecular spectrum of tissues. (LLM, conf=0.83)

  cites [4] Gebetsberger J., Wyss L., Mleczko A. M., Reuther J., Polacek N., A tRNA-derived fragment competes with mRNA for ribosome binding and regulates translation during stress. RNA Biol. 14, 1364– 1373 (2017). 27892771 PMC5711459 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [17] Faridani O. R., Single-cell sequencing of the small-RNA transcriptome. Nat. Biotechnol. 34, 1264– 1266 (2016). 27798564 source

In the paper

“Small noncoding RNAs (ncRNAs) are a large family of endogenously expressed transcripts, 18 to 200 nt long”

What the sources say

• Partly supported

  The Introduction (page unavailable) describes endogenous small RNAs as a larger class and identifies lin-4 and let-7 products as noncoding RNAs about 22 nt long. It does not give an 18–200 nt range for small ncRNAs generally, so the stated length range is unsupported by this source. (LLM, conf=0.84)

  cites [1] Bartel D. P., Metazoan microRNAs. Cell 173, 20– 51 (2018). 29570994 PMC6091663 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction describes several classes of small ncRNAs, and the discussion of miRNAs calls them cellularly encoded. The discussion of lncRNAs places long ncRNAs above 200 nt, but our copy does not define small ncRNAs as 18–200 nt or establish the 18-nt lower bound (searched for the range and its endpoints). (LLM, conf=0.84)

  cites [2] Cech T. R., Steitz J. A., The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157, 77– 94 (2014). 24679528 sourceExperimental — accuracy not yet measured

In the paper

“today small ncRNAs are believed to be involved in nearly all developmental and pathological processes in mammals (2–4)”

What the sources say

• Partly supported

  The review says miRNAs contribute importantly to developmental, differentiation, and disease processes (indexed passage, section labeled Abstract; no page provided). It does not establish that small ncRNAs are involved in nearly all such processes in mammals; that breadth goes beyond the passage. (LLM, conf=0.86)

  cites [2] Cech T. R., Steitz J. A., The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157, 77– 94 (2014). 24679528 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [3] Esteller M., Non-coding RNAs in human disease. Nat. Rev. Genet. 12, 861– 874 (2011). 22094949 source
• Partly supported

  The Introduction (page not provided) describes ncRNAs as important regulators of gene expression and discusses the regulatory roles of small RNA fragments. It does not say that small ncRNAs are involved in nearly all developmental and pathological processes in mammals; the Discussion instead focuses on a stress-responsive tRNA fragment in an archaeon. (LLM, conf=0.82)

  cites [4] Gebetsberger J., Wyss L., Mleczko A. M., Reuther J., Polacek N., A tRNA-derived fragment competes with mRNA for ribosome binding and regulates translation during stress. RNA Biol. 14, 1364– 1373 (2017). 27892771 PMC5711459 sourceExperimental — accuracy not yet measured

In the paper

“numerous studies have revealed the direct involvement of various small ncRNAs in regulation of gene expression at the levels of posttranscriptional mRNA processing (5–7) and ribosome biogenesis (8)”

What the sources say

• Supported

  The citation is attached to posttranscriptional mRNA processing, not ribosome biogenesis. The Introduction identifies snRNAs as components of spliceosomes, and the Discussion reports that immature snRNAs impair spliceosomes and cause genome-wide splicing defects. This supports the claimed involvement of small ncRNAs in mRNA processing. (LLM, conf=0.90)

  cites [5] Becker D., Nuclear pre-snRNA export is an essential quality assurance mechanism for functional spliceosomes. Cell Rep. 27, 3199– 3214.e3 (2019). 31189105 source
• Partly supported

  The Introduction and ‘Overview of miRNA function’ (pages unavailable) describe microRNAs regulating gene expression after transcription through translational repression and mRNA decay, including deadenylation and decapping. The cited paper does not establish the broader claim about various small ncRNAs or address ribosome biogenesis. (LLM, conf=0.82)

  cites [6] Gebert L. F. R., MacRae I. J., Regulation of microRNA function in animals. Nat. Rev. Mol. Cell Biol. 20, 21– 37 (2019). 30108335 PMC6546304 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page unavailable) links tRNA-derived fragments to post-transcriptional transcript regulation and reports their Ago loading, but it treats their targeting of other RNA transcripts as an expectation rather than a direct finding of this study. The cited passages do not establish the broader claim about various small ncRNAs or address ribosome biogenesis. (LLM, conf=0.82)

  cites [7] Telonis A. G., Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget 6, 24797– 24822 (2015). 26325506 PMC4694795 sourceExperimental — accuracy not yet measured
• Supported

  Citation (8) is attached to the ribosome-biogenesis part of the sentence, not the mRNA-processing part. The BACKGROUND section says snoRNPs act in the nucleolus, where ribosome biogenesis takes place, and that a subset is required for pre-rRNA cleavage. (LLM, conf=0.90)

  cites [8] Reichow S. L., Hamma T., Ferré-D’Amaré A. R., Varani G., The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 35, 1452– 1464 (2007). 17284456 PMC1865073 source

In the paper

“snoRNA and snRNA are believed to yield incomplete recovery in small RNA-seq experiments due to their secondary structure (32).”

What the sources say

• Partly supported

  The Discussion (page not provided) says size selection favors shorter, less structured box C/D snoRNAs over longer H/ACA snoRNAs, supporting structure-related incomplete recovery for some snoRNAs. The Results (page not provided) also report biased detection of small noncoding RNAs, but do not establish that snRNAs are incompletely recovered because of their secondary structure. (LLM, conf=0.84)

  cites [32] Boivin V., Simultaneous sequencing of coding and noncoding RNA reveals a human transcriptome dominated by a small number of highly expressed noncoding genes. RNA 24, 950– 965 (2018). 29703781 PMC6004057 sourceExperimental — accuracy not yet measured

In the paper

“Aberrant expression of small ncRNAs, in turn, has been associated with diseases such as cancer, autoimmune disease, and several neurodegenerative disorders (9, 10).”

What the sources say

• ?Not checked — no full text of the sourcecites [9] Keller A., Toward the blood-borne miRNome of human diseases. Nat. Methods 8, 841– 843 (2011). 21892151 source
• Partly supported

  The “Strictly developmental regulation” section links miR-29 to tumor suppression and its loss to sporadic Alzheimer’s disease; “Aging as extended development” also discusses miR-34a in neuroblastoma and an Alzheimer’s mouse model. These passages support associations with cancer and one neurodegenerative disorder, but the copy does not support the claim about autoimmune disease or several neurodegenerative disorders. Page numbers are not provided in the indexed passages. (LLM, conf=0.87)

  cites [10] Somel M., MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 20, 1207– 1218 (2010). 20647238 PMC2928499 sourceExperimental — accuracy not yet measured

In the paper

“with some being shown to be expressed in a tissue- (16), cell type- (17), or even cell state-specific manner (18)”

What the sources say

• ?Not checked — no full text of the sourcecites [16] Landgraf P., A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401– 1414 (2007). 17604727 PMC2681231 source
• ?Not checked — no full text of the sourcecites [17] Faridani O. R., Single-cell sequencing of the small-RNA transcriptome. Nat. Biotechnol. 34, 1264– 1266 (2016). 27798564 source
• Supported

  Citation (18) is attached to the cell state-specific part of the sentence. In Results > Validation of novel miRNAs by qRT-PCR (page not specified), the paper reports that several miRNAs decrease during differentiation of rat embryonic and induced pluripotent stem cells, supporting expression that varies by cell state. (LLM, conf=0.93)

  cites [18] Sherstyuk V. V., Genome-wide profiling and differential expression of microRNA in rat pluripotent stem cells. Sci. Rep. 7, 2787 (2017). 28584262 PMC5459850 source

In the paper

“that play a crucial role in regulating cell function (1, 2)”

What the sources say

• Partly supported

  The Introduction describes microRNAs as small regulatory RNAs, and “Biological Importance of miRNAs” says they influence diverse cellular functions. The paper supports the claim for microRNAs, but the citing sentence extends it to small noncoding RNAs generally. (LLM, conf=0.82)

  cites [1] Bartel D. P., Metazoan microRNAs. Cell 173, 20– 51 (2018). 29570994 PMC6091663 sourceExperimental — accuracy not yet measured
• Supported

  The Introduction describes small ncRNAs, including miRNAs, as important in regulating gene expression. The paper also describes small RNAs that regulate translation, supporting the broader paraphrase that they help regulate cell function. Page numbers are not provided in our copy. (LLM, conf=0.91)

  cites [2] Cech T. R., Steitz J. A., The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157, 77– 94 (2014). 24679528 source

In the paper

“We identified both well-described brain-specific miRNAs, such as mir-9, mir-124, mir-219, mir-338 (16, 24, 33), as well as those which are missing from existing catalogs, such as mir-666, mir-878, mir-433, etc.”

What the sources say

• ?Not checked — no full text of the sourcecites [16] Landgraf P., A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401– 1414 (2007). 17604727 PMC2681231 source
• ?Could not verify

  The Results sections on diverse microRNA expression and novel human microRNAs discuss cell-specific expression and newly identified candidates, but do not identify miR-9, miR-124, miR-219, or miR-338 as brain-specific, or miR-666, miR-878, or miR-433 as missing from catalogs. Searches for those names and for brain-specific microRNAs found no passage establishing the attributed examples; page numbers were not available in our copy. (LLM, conf=0.72)

  cites [24] McCall M. N., Toward the human cellular microRNAome. Genome Res. 27, 1769– 1781 (2017). 28877962 PMC5630040 sourceExperimental — accuracy not yet measured
• Supported

  The citation follows the list of well-described brain-specific miRNAs, not the citing authors’ subsequent claim about miRNAs missing from catalogs. In Results, “Clustering of tissue patterns and analysis of miRNA families,” the source reports brain-specific expression of all four listed miRNAs. (LLM, conf=0.93)

  cites [33] Ludwig N., Distribution of miRNA expression across human tissues. Nucleic Acids Res. 44, 3865– 3877 (2016). 26921406 PMC4856985 source

In the paper

“we could identify that muscle-specific mir-133a-2 is expressed in cardiomyocytes, while mir-148a is expressed in hepatocytes and duct cells (Fig. 6 C and D) and mir-194–2 comes from the enterocytes in the gut (24, 25).”

What the sources say

• ?Could not verify

  The Results section discusses cell-specific microRNA expression, but the passages in our copy do not identify miR-133a-2 in cardiomyocytes, miR-148a in hepatocytes or duct cells, or miR-194-2 in gut enterocytes. Searches for each named microRNA with its claimed cell type found no passage establishing those associations; page numbers were not available. (LLM, conf=0.72)

  cites [24] McCall M. N., Toward the human cellular microRNAome. Genome Res. 27, 1769– 1781 (2017). 28877962 PMC5630040 sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results sections on cell ontology and pri-miRNA expression report cell-type patterns, but not the claimed pairings: they name miR-122-5p in hepatocytes and mir-208a in heart, rather than the miRNAs in the citing sentence. Searches for mir-133a-2, mir-148a, and mir-194-2 with their claimed cell types found no passage establishing those expression patterns, including the gut-enterocyte claim nearest the citation. (LLM, conf=0.74)

  cites [25] de Rie D..; FANTOM Consortium, An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat. Biotechnol. 35, 872– 878 (2017). 28829439 PMC5767576 sourceExperimental — accuracy not yet measured

In the paper

“Several groups have observed a sex bias in the levels of miRNA in blood, cancer tissues, and human lymphoblastoid cell lines (57, 58).”

What the sources say

• Supported

  The Abstract reports prior findings of sex differences in miRNA expression and concentration, and cites work on gender-dependent isomiR expression in human lymphoblastoid cell lines (References; isomiRs are miRNA variants). The Results section, “Expression and functional analysis in the same tissues between males and females,” reports sex-dependent miRNA expression in cancer tissues. The paper therefore supports the sentence as a summary of findings across studies, rather than as a description of samples it analyzed itself. (LLM, conf=0.84)

  cites [57] Guo L., Zhang Q., Ma X., Wang J., Liang T., miRNA and mRNA expression analysis reveals potential sex-biased miRNA expression. Sci. Rep. 7, 39812 (2017). 28045090 PMC5206641 source
• Partly supported

  The Discussion reports gender-dependent isomiR expression patterns in human lymphoblastoid cell lines. But the Results section says that no isomiR showed a statistically significant male–female expression difference within any of the five populations, so the paper does not establish a direct sex bias in levels within a population. It does not study blood or cancer tissues. (LLM, conf=0.85)

  cites [58] Loher P., Londin E. R., Rigoutsos I., IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies. Oncotarget 5, 8790– 8802 (2014). 25229428 PMC4226722 sourceExperimental — accuracy not yet measured

In the paper

“Recent efforts in profiling of the most studied types of small ncRNA, miRNA, across cells and tissues demonstrated the existence of tissue- and cell type-specific short noncoding transcripts (16, 24, 25, 33).”

What the sources say

• ?Not checked — no full text of the sourcecites [16] Landgraf P., A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401– 1414 (2007). 17604727 PMC2681231 source
• Supported

  The Abstract reports profiling microRNA expression across 46 primary cell types, 42 cell lines, and 26 tissues, identifying both specific and ubiquitous patterns. The Results section, “Diverse microRNAs expression patterns,” reports that 94 of 320 highly expressed microRNAs occurred in only one normal cell class, supporting cell-type specificity; the Discussion also describes cell-specific expression patterns. (LLM, conf=0.93)

  cites [24] McCall M. N., Toward the human cellular microRNAome. Genome Res. 27, 1769– 1781 (2017). 28877962 PMC5630040 source
• Partly supported

  The Results sections ‘Expression variability of miRNAs in human primary cells’ and ‘Cell ontology analysis’ describe profiling miRNAs across primary cells and tissues and report miRNAs enriched in particular cell types. The passages establish cell-type specificity, but do not separately demonstrate tissue-specific expression. (LLM, conf=0.81)

  cites [25] de Rie D..; FANTOM Consortium, An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat. Biotechnol. 35, 872– 878 (2017). 28829439 PMC5767576 sourceExperimental — accuracy not yet measured

In the paper

“the AGO-CLIP, while often used as a “gold standard” of miRNA validation (24)”

What the sources say

• Partly supported

  The Results (Novel human microRNAs; page unavailable) use Argonaute CLIP-seq data to narrow the list of putative miRNAs, supporting its use as validation evidence. The paper does not say AGO-CLIP is often used or regarded as a gold standard; the Discussion says the resulting candidates are not definitive miRNAs and require further in vivo evidence. (LLM, conf=0.85)

  cites [24] McCall M. N., Toward the human cellular microRNAome. Genome Res. 27, 1769– 1781 (2017). 28877962 PMC5630040 sourceExperimental — accuracy not yet measured

In the paper

“Batch effects were corrected using limma R package (79).”

What the sources say

• Partly supported

  The Introduction and Results > User-interface identify limma as an R-based package. Results > Preprocessing microarray data says its normalization methods remove systematic technical differences between assays, but the passages found do not describe correction of batch effects specifically. The cited paper also cannot establish that the citing authors performed that correction. (LLM, conf=0.78)

  cites [79] Ritchie M. E., Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015). 25605792 PMC4402510 sourceExperimental — accuracy not yet measured

In the paper

“Since the abundance of these specific fragments has been shown to correlate with the levels of functional angiogenin in the cell (54)”

What the sources say

• Supported

  In Results, “Effect of ANG on cellular tRF levels” (page unavailable), the authors report that particular tRFs rose sharply after ANG treatment, especially in cells lacking the ANG inhibitor RNH1. This supports the claimed relationship between the abundance of specific tRFs and functional ANG in the cells studied. (LLM, conf=0.87)

  cites [54] Thomas S. P., Hoang T. T., Ressler V. T., Raines R. T., Human angiogenin is a potent cytotoxin in the absence of ribonuclease inhibitor. RNA 24, 1018– 1027 (2018). 29748193 PMC6049508 source

In the paper

“another miRNA, mir-340, was reported to be down-regulated in response to elevated androgen levels (60).”

What the sources say

• Supported

  In the ‘Androgen regulation of miR expression’ section, the review reports that miR-340 was downregulated by androgen in androgen-stimulated LNCaP cells. This supports the cited claim; the reported setting is a prostate cancer cell line. (LLM, conf=0.92)

  cites [60] Fletcher C. E., Dart D. A., Bevan C. L., Interplay between steroid signalling and microRNAs: Implications for hormone-dependent cancers. Endocr. Relat. Cancer 21, R409– R429 (2014). 25062737 source

In the paper

“We have recently demonstrated that the current miRbase annotation of mammalian miRNA remains incomplete but can be readily expanded with the help of emerging small RNA-seq data (46).”

What the sources say

• Partly supported

  The Discussion (page not available in our copy) estimates that miRBase V22 contains about half of the true human mature miRNAs and reports validated miRNAs not yet annotated there. The Results describe using small RNA-seq data to assess novel candidates, but many failed the study’s quality criteria. The paper supports an incomplete human annotation and the potential to expand it; it does not establish that mammalian annotations generally can be readily expanded from sequencing data alone. (LLM, conf=0.86)

  cites [46] Alles J., An estimate of the total number of true human miRNAs. Nucleic Acids Res. 47, 3353– 3364 (2019). 30820533 PMC6468295 sourceExperimental — accuracy not yet measured

In the paper

“Three out of eight female-dominant miRNAs: mir-182, mir-148a, and mir-145a, were also shown previously to be estrogen regulated (59)”

What the sources say

• Partly supported

  In “E2 Regulation of miRNAs in Animal Studies” (page unavailable), the review reports estrogen-related changes in miR-148a and miR-145. It does not identify miR-145a specifically, and no passage found for miR-182 establishes that it is estrogen regulated. The source therefore does not support all three named miRNAs. (LLM, conf=0.87)

  cites [59] Klinge C. M., Estrogen regulation of microRNA expression. Curr. Genomics 10, 169– 183 (2009). 19881910 PMC2705850 sourceExperimental — accuracy not yet measured

In the paper

“Among these are ncRNAs known to be expressed in a large number of cell types, such as let-7d-3p, miR-320-3p (25), ncRNAs the cell type specificity of which is still unknown, such as Snord4a and Snord55, as well as those known to be expressed in the cell types that are abundant in all tissues (like endothelial miR-151-5p)”

What the sources say

• ?Could not verify

  The citation is attached to the examples let-7d-3p and miR-320-3p, not to Snord4a, Snord55, or endothelial miR-151-5p. The Results section on cell ontology analysis reports that some miRNAs are broadly expressed, but does not identify either cited example as such. Searches for both miRNA names found no passage establishing their expression across many cell types. (LLM, conf=0.72)

  cites [25] de Rie D..; FANTOM Consortium, An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat. Biotechnol. 35, 872– 878 (2017). 28829439 PMC5767576 sourceExperimental — accuracy not yet measured

In the paper

“The precise biological function of Rny1 and Rny3 is so far undefined, although they have been suggested to maintain RNA stability (38).”

What the sources say

• Partly supported

  The section on Y RNAs and RoRNPs says Y RNAs have a role in RNA stability, while the Introduction says the precise cellular function of RoRNPs is unclear. Neither passage makes those statements specifically about Rny1 and Rny3, so the claim’s gene-specific attribution is not supported by this copy. (LLM, conf=0.83)

  cites [38] Kowalski M. P., Krude T., Functional roles of non-coding Y RNAs. Int. J. Biochem. Cell Biol. 66, 20– 29 (2015). 26159929 PMC4726728 sourceExperimental — accuracy not yet measured

In the paper

“fragments of either mature of precursor tRNA molecules enzymatically cleaved by angiogenin (Ang), Dicer, RNaseZ, and RNaseP (7, 53)”

What the sources say

• Partly supported

  The Introduction says tRFs can arise from mature or precursor tRNAs and describes roles for angiogenin, Dicer, and RNase Z, with Dicer dependence limited to several organisms. It does not identify RNase P as an enzyme producing tRFs, so the four-enzyme list is not fully supported. (LLM, conf=0.87)

  cites [7] Telonis A. G., Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget 6, 24797– 24822 (2015). 26325506 PMC4694795 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion (page not available in our copy) support tRFs arising from mature tRNA and pre-tRNA, and identify ELAC2 as the enzyme generating the pre-tRNA-derived tRF-1001. The Discussion says the enzyme responsible for mature-tRNA-derived tRF-5 and tRF-3 is unclear; it describes angiogenin-generated fragments as different from those studied here. Our copy does not identify Dicer, RNaseZ, or RNaseP as enzymes generating these tRFs. (LLM, conf=0.88)

  cites [53] Lee Y. S., Shibata Y., Malhotra A., Dutta A., A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 23, 2639– 2649 (2009). 19933153 PMC2779758 sourceExperimental — accuracy not yet measured

In the paper

“which correspond to 60%, 53%, 39%, 96%, 92%, 100%, and 34% of annotated transcripts of each respective class”

In the paper

“miRNA was the most abundant small ncRNA type in our libraries, followed by snoRNA, snRNA, and tRFs”

In the paper

“The number of distinct ncRNA greatly varied across tissues; for example, lymphoid tissues (lung, spleen, and bone marrow) contained the largest number of distinct ncRNA, while pancreas and liver contained the fewest”

In the paper

“We have also discovered that certain miRNAs are broadly sexually dimorphic, while other show sex bias in the context of specific tissues.”

In the paper

“we mapped tissue-specific as well as broadly transcribed small ncRNA attributed to five different classes and spanning a large spectrum of expression levels”

In the paper

“the detected tRFs were intergenic, snoRNAs were of intronic origin, snRNAs and scaRNAs were intronic and intergenic (63/35% and 64/36%, respectively), and miRNAs were transcribed from either introns (53%), exons (11%), or intergenic regions (11%)”

In the paper

“Each library yielded ∼5 to 20 million reads mapping to the mouse genome, out of which, on average ∼7 million mapped to the exons of small ncRNA genes (Materials and Methods), resulting in a total of ∼100 million ncRNA reads per tissue”

In the paper

“we identified a total of 1,317 distinct miRNA, 733 snRNA, 583 snoRNA, 25 scaRNA, 346 tRNA, 22 mitochondrial tRNA, and 193 other miscellaneous small ncRNA genes”

In the paper

“mtRFs followed a similar trend of fragment shift. We found 5′tRFs of proline-transferring mt-Tp in the heart and 5′tRFs of asparagine-transferring mt-Tn in the liver, while within other tissues we detected different fragment types of these tRNAs”

In the paper

“we identified novel miRNAs (17_8620, 4_6440, 9_15723) that are supported by AGO-CLIP data, prior reports, or both, but for which we could not confirm the existence through RT-qPCR”

In the paper

“In the case of nuclear tRFs, the vast majority of fragments in each tissue were attributed to glycine, glutamine, valine, and lysine tRNA, with the intestine containing the largest amounts of the respective 5′tR-halves.”

In the paper

“Differential expression analysis on putative novel miRNAs identified six miRNAs to be also expressed in a sex-specific manner. Strikingly, all six were male-dominant, with one of them even found to be consistently up-regulated in two tissues, male muscle and pancreas”

In the paper

“we identified mir-187 and mir-142 to be expressed in microglia”

In the paper

“Examples of other miRNAs previously unknown to be tissue-specific include mir-499 in the heart, mir-3073b in the kidney, and mir-215 and mir-194 in the intestine”

In the paper

“our SVM model accurately classified postnatal forebrain, midbrain, hindbrain, and neural tube as brain tissue, as well as accurately inferred the tissue types for heart, intestine, kidney, liver, and muscle samples, yielding an overall accuracy of 0.96”

In the paper

“Using the top 400 ncRNAs identified in our analysis as tissue-specific, we correlated average ATAC-seq activity scores and ncRNA levels across eight tissues for which both types of data were available. We observed a strong correlation of both measurements for the brain, liver, and heart, and a weaker correlation for kidney and mixed scores between spleen, bone marrow, and lung”

In the paper

“we detected the presence of telomerase RNA component (Terc) in analyzed somatic tissues, with the highest levels seen in the bone marrow and spleen.”

In the paper

“predominantly present in either glutamatergic (Snord53, mir-802)”

In the paper

“we observed that mouse bone marrow and spleen had the highest correlation with human B cells, T cells, dendritic cells, and macrophages (0.5 < rs < 0.6), muscle correlated the most with myoblasts and myotubes (rs = 0.47), while brain correlated best with neural stem cells, spinal cord, and pineal and pituitary glands (rs = 0.49)”

In the paper

“We observed this phenomenon on the de novo identified miRNA 14_6588, whose coordinates strictly overlap with mir-802a and that is only present in the brain.”

In the paper

“we found miR-423, up-regulated in male lung and bone marrow, to negatively correlate with its target, estrogen-related receptor gamma (Esrrg) (rs = −0.9, FDR < 0.1)”

In the paper

“we found that in the lung, mir-449c in expressed in alveolar macrophages, mir-34b and mir-34c in type II pneumocytes (Fig. 6E), and mir-155 is found in B cells”

In the paper

“the genomic coordinates of this miRNA, 14_6588, matched the coordinates of another, annotated one, mir-802a. Unlike mir-802a, however, 14_6588 is transcribed from the negative DNA strand and is only present in the brain”

In the paper

“we found that FANTOM5 embryonic and neonatal cerebellum tissues strongly correlated with our brain samples (rs = 0.89 to 0.9), while erythroid cells had the strongest correlation with spleen and bone marrow (rs = 0.93)”

In the paper

“While the majority of ntRNA fragments were 33 nt long, mtRNA fragments spanned a large size range of 18 to 54 nt”

In the paper

“Similar to annotated transcripts, novel miRNAs demonstrate a spectrum of tissue specificity with some being ubiquitously expressed, while others are only present in one tissue”

In the paper

“mir-124a-3, mir-1983, mir-212, and others in neurons (Fig. 6G)”

In the paper

“We found that the majority of putative miRNAs are present in only one tissue (312), but a small number (4) are found in all 11 tissues”

In the paper

“Kidney and lung contained the highest number of sex-biased miRNAs (27 and 18, respectively), while only two were detected in the heart, five in the muscle, and seven in the brain”

In the paper

“mouse Rnu11 and Scarna6 are preferentially found in lymphoid tissues, while three snRNAs of unverified function, Gm25793, Gm22448, and Gm23814, are specific to the brain”

In the paper

“we identified Snord17 and mir-700 in macrophages”

In the paper

“Out of these 400, nearly one-quarter are specific to the brain, with some being uniquely expressed within the tissue”

In the paper

“Some of them are globally sexually dimorphic, while the majority are sex-biased only within a specific tissue.”

In the paper

“mir-155 is found in B cells and even correlates with its maturation status (Fig. 6F)”

In the paper

“For many miRNAs, we generally observed the dominance of either 3p or 5p arm, while for some we also detected high levels of both arms present in one or multiple tissues”

In the paper

“we also identified Snora35 (MBI-36) and Snord116 (MBII-85), known to be involved in neurodevelopmental disorders (34), to be brain exclusive (TSI = 1).”

What the sources say

• ?Not checked — no full text of the sourcecites [34] Gallagher R. C., Pils B., Albalwi M., Francke U., Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader–Willi syndrome. Am. J. Hum. Genet. 71, 669– 678 (2002). 12154412 PMC379204 source

In the paper

“Mammalian cells express several classes of small ncRNA, including microRNA (miRNA) (11), small interfering RNAs (siRNA), small nucleolar RNAs (snoRNA) (12), small nuclear RNA (snRNA) (13), PIWI-interacting RNA (piRNA) (14), and tRNA-derived small RNAs (tRFs) (15)”

What the sources say

• ?Not checked — no full text of the sourcecites [11] Ha M., Kim V. N., Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15, 509– 524 (2014). 25027649 source
• ?Not checked — no full text of the sourcecites [12] Matera A. G., Terns R. M., Terns M. P., Non-coding RNAs: Lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8, 209– 220 (2007). 17318225 source
• ?Not checked — no full text of the sourcecites [13] Kiss T., Biogenesis of small nuclear RNPs. J. Cell Sci. 117, 5949– 5951 (2004). 15564372 source

In the paper

“Small ncRNA plays an indispensable role in shaping cellular identity in health and disease by orchestrating vital cellular processes and altering the expression of protein-coding genes (12).”

What the sources say

• ?Not checked — no full text of the sourcecites [12] Matera A. G., Terns R. M., Terns M. P., Non-coding RNAs: Lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8, 209– 220 (2007). 17318225 source

In the paper

“it proved to be more inclusive for the reads uniquely mapping within the miRNA exon but missing one base at the 5′ prime end of the molecule and more strict in counting reads mapping elsewhere in the genome, for which the levels were consistently overestimated by the other method.”

In the paper

“the genomic location of a novel miRNA might match with that of a previously annotated one, while the molecule itself could be transcribed from an opposite DNA strand.”

In the paper

“All procedures followed animal care and biosafety guidelines approved by Stanford University’s Administrative Panel on Laboratory Animal Care and Administrative Panel of Biosafety.”

In the paper

“miRNA has been previously used to train classifiers capable of differentiating cancer/tissue types (71).”

What the sources say

• ?Not checked — no full text of the sourcecites [71] Sherafatian M., Tree-based machine learning algorithms identified minimal set of miRNA biomarkers for breast cancer diagnosis and molecular subtyping. Gene 677, 111– 118 (2018). 30055304 source

In the paper

“We normalized and scaled train and test datasets separately.”

In the paper

“We counted a putative miRNA as “supported” if it had >5 AGO-CLIP counts.”

In the paper

“For independent validation, we performed RT-qPCR using custom Small RNA TaqMan probes (Life Technologies; catalog #4398987) designed on the star consensus sequence reported by miRDeep2.”

In the paper

“Only miRNAs supported by >5 reads were reported in this study.”

In the paper

“RNA integrity was assessed using Agilent Bioanalyzer using RNA 6000 pico kit”

In the paper

“The accuracy was computed using 10-fold cross-validation procedure.”

In the paper

“P values obtained from the LRT test were corrected using Benjamini–Hochberg procedure to obtain an FDR estimate of tissue specificity scores for each gene.”

In the paper

“To test for the NULL hypothesis, we performed a permutation test in which we randomly reassigned the sex labels to 14 samples across each tissue and plotted the distribution of DESeq2 P values computed for the two groups (i.e., female and male) (SI Appendix, Fig. S7A).”

In the paper

“We analyzed tissue and sex specificity of identified miRNAs based on transcripts supported by at least 50 sequencing reads across all samples.”

In the paper

“We used Benjamini–Hochberg-corrected P values (FDR) to assess the statistical significance of the computed DE scores (Fig. 5 and SI Appendix, Fig. S7A).”

In the paper

“In this work, we show that this phenomenon extends beyond one ncRNA class and involves not only tissue-specific but also sex-specific ncRNA expression.”

In the paper

“Only targets present in two or more databases were used.”