A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome

Fromm, Bastian; Billipp, Tyler; Peck, Liam E.; Johansen, Morten; Tarver, James E.; King, Benjamin L.; Newcomb, James M.; Sempere, Lorenzo F.; Flatmark, Kjersti; Hovig, Eivind; Peterson, Kevin J.

doi:10.1146/annurev-genet-120213-092023

Cited by 479 publications

(554 citation statements)

References 158 publications

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“…Serum and CSF xenomiR levels were also similar when considering only CSF from healthy individuals (χ 2 test, P-value = 0.476). To demonstrate that our findings are not biased by the choice of miRNA database, we repeated the analysis using only the highly curated miRNAs from MirGeneDB (Fromm et al 2015). For zebrafish, chicken, and mouse we find exactly the same amount of miRNAs reported using miRBase and MirGeneDB (Supplemental Fig.…”

Section: Xenomirs Are Commonly Present In Body Fluidssupporting

confidence: 52%

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Kang

Bang-Berthelsen

Holm

et al. 2017

RNA

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miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake.

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Section: Xenomirs Are Commonly Present In Body Fluidssupporting

confidence: 52%

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Kang

Bang-Berthelsen

Holm

et al. 2017

RNA

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show abstract

“…Given the regulatory divergence between the species studied here, it is perhaps not surprising that we observe very limited evolutionary conservation of sex-biased miRNA expression across species. In fact, we were not able to identify a single case in which an orthologous (Kozomara and Griffiths-Jones 2014;Fromm et al 2015) mature miRNA showed significant bias in the same direction and in the same somatic tissue in two species (Supplemental Fig. S5).…”

Section: Discussionmentioning

confidence: 92%

Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation

et al. 2017

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Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.

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“…The 795 human and 502 mouse (Figure S1) pre-miRNAs satisfying at least 4 out of the 5 high-confidence criteria were defined as the FANTOM5 robust set, and the remaining 1076 human and 684 mouse pre-miRNAs as the permissive set (Table S4 and S5). The robust set encompasses 735 human and 438 mouse mature miRNAs, and covers more than 90% of the high-confidence pre-miRNAs in miRBase (Figures S2 and S3), 90% of miRNAs well-characterized in the scientific literature (Figure S4), as well as 91% (human) and 88% (mouse) of pre-miRNAs included in the manually curated MirGeneDB database 20 (Figure S5). …”

Section: Resultsmentioning

confidence: 99%

An integrated expression atlas of miRNAs and their promoters in human and mouse

Rie¹,

Abugessaisa²,

et al. 2017

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MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

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A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome

Cited by 479 publications

References 158 publications

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation

An integrated expression atlas of miRNAs and their promoters in human and mouse

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