Sequence features associated with microRNA strand selection in humans and flies

Hu, Hai; Zheng, Yanyan; Xu, Ying; Hu, Hao; Menzel, Corinna; Zhou, Yan; Chen, Wei; Khaitovich, Philipp

doi:10.1186/1471-2164-10-413

Cited by 151 publications

(125 citation statements)

References 52 publications

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“…miRNAs from both arms, with occasional tissue-specific differences in the preferred arm Most canonical miRNA genes produced one dominant mature miRNA species, from either the 59 or 39 arm of the pre-miRNA hairpin, with an overall tendency to derive from the 59 arm (Table 1), as reported for previously annotated human miRNAs (Hu et al 2009). Some, however, yielded a similar number of reads from both arms, suggesting that the two species enter the silencing complex with similar frequencies.…”

Section: General Features Of Mammalian Mirnasmentioning

confidence: 80%

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

Chiang

Schoenfeld²,

Ruby³

et al. 2010

Genes Dev.

750

756

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MicroRNAs (miRNAs) are small regulatory RNAs that derive from distinctive hairpin transcripts. To learn more about the miRNAs of mammals, we sequenced 60 million small RNAs from mouse brain, ovary, testes, embryonic stem cells, three embryonic stages, and whole newborns. Analysis of these sequences confirmed 398 annotated miRNA genes and identified 108 novel miRNA genes. More than 150 previously annotated miRNAs and hundreds of candidates failed to yield sequenced RNAs with miRNA-like features. Ectopically expressing these previously proposed miRNA hairpins also did not yield small RNAs, whereas ectopically expressing the confirmed and newly identified hairpins usually did yield small RNAs with the classical miRNA features, including dependence on the Drosha endonuclease for processing. These experiments, which suggest that previous estimates of conserved mammalian miRNAs were inflated, provide a substantially revised list of confidently identified murine miRNAs from which to infer the general features of mammalian miRNAs. Our analyses also revealed new aspects of miRNA biogenesis and modification, including tissue-specific strand preferences, sequential Dicer cleavage of a metazoan precursor miRNA (pre-miRNA), consequential 59 heterogeneity, newly identified instances of miRNA editing, and evidence for widespread pre-miRNA uridylation reminiscent of miRNA regulation by Lin28.[Keywords: MicroRNA; miRNA biogenesis; noncoding RNA genes; high-throughput sequencing] Supplemental material is available at http://www.genesdev.org.

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Section: General Features Of Mammalian Mirnasmentioning

confidence: 80%

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

Chiang

Schoenfeld²,

Ruby³

et al. 2010

Genes Dev.

750

756

View full text Add to dashboard Cite

show abstract

“…Typically, one strand of this mature miRNA duplex, termed the guide strand, associates with the RNA-induced silencing complex (RISC). While it is generally believed that upon incorporation into the RISC complex, the other strand (the passenger strand) is unwound from the guide strand and degraded, there is evidence that in some cases, both strands of the miRNA duplex are functional (13). MiRNA-RISC complexes interact with mRNA targets through partial sequence complementation, typically within the 3' untranslated region of target mRNAs.…”

Section: Circulating Micrornas: New Biomarkers In Diagnosis Prognosimentioning

confidence: 99%

Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (Review)

Allegra

Alonci

Campo

et al. 2012

International Journal of Oncology

321

208

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“…Most of the early characterization of miRNAs focused on the guide strands (usually the 5p), because these were typically found to be more abundant than their miRNA * counterparts in humans (Hu et al 2009). However, many miRNA * strands have conserved seed sequences and have been isolated from RISC complexes, therefore suggesting that they are functional (Okamura et al 2008a;Yang et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Synthetic pre-microRNAs reveal dual-strand activity of miR-34a on TNF-α

Guennewig

Roos

Dogar

et al. 2013

RNA

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Functional microRNAs (miRNAs) are produced from both arms of their precursors (pre-miRNAs). Their abundances vary in contextdependent fashion spatiotemporarily and there is mounting evidence of regulatory interplay between them. Here, we introduce chemically synthesized pre-miRNAs (syn-pre-miRNAs) as a general class of accessible, easily transfectable mimics of premiRNAs. These are RNA hairpins, identical in sequence to natural pre-miRNAs. They differ from commercially available miRNA mimics through their complete hairpin structure, including any regulatory elements in their terminal-loop regions and their potential to introduce both strands into RISC. They are distinguished from transcribed pre-miRNAs by their terminal 5′ hydroxyl groups and their precisely defined terminal nucleotides. We demonstrate with several examples how they fully recapitulate the properties of pre-miRNAs, including their processing by Dicer into functionally active 5p-and 3p-derived mature miRNAs. We use syn-pre-miRNAs to show that miR-34a uses its 5p and 3p miRNAs in two pathways: apoptosis during TGF-β signaling, where SIRT1 and SP4 are suppressed by miR-34a-5p and miR-34a-3p, respectively; and the lipopolysaccharide (LPS)-activation of primary human monocyte-derived macrophages, where TNF (TNFα) is suppressed by miR-34a-5p indirectly and miR-34a-3p directly. Our results add to growing evidence that the use of both arms of a miRNA may be a widely used mechanism. We further suggest that syn-pre-miRNAs are ideal and affordable tools to investigate these mechanisms.

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Sequence features associated with microRNA strand selection in humans and flies

Cited by 151 publications

References 52 publications

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes

Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (Review)

Synthetic pre-microRNAs reveal dual-strand activity of miR-34a on TNF-α

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