Mammalian microRNAs: experimental evaluation of novel and previously annotated genes.

By H. R. Chiang, L. Schoenfeld, J. Ruby, V. Auyeung, Noah Spies, Daehyun Baek, W. K. Johnston, C. Russ, Shujun J Luo, Joshua Babiarz and 4 more. Genes & Development, 2010

847 citations recorded by the source corpus.

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 5' heterogeneity, newly identified instances of miRNA editing, and evidence for widespread pre-miRNA uridylation reminiscent of miRNA regulation by Lin28.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/be98cfa888e7d11b449f09f377ec625ed1fe07ed

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Citations in the corpus

Predicting effective microRNA target sites in mammalian mRNAs (2015, background): “…which have 11–12 contiguous Watson–Crick pairs to the center of the miRNA ( Shin et al., 2010 ), and cleavage sites, which have the very extensive pairing required for Argonaute-catalyzed slicing of the mRNA ( Yekta et al., 2004 ; Davis et al., 2005 ; Karginov et al., 2010 ; Shin et al., 2010 ).”
Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families (2017, background): “Sau-50 (RF02391) failed protein-coding check, and mir-689 (RF00871) was identified as an rRNA fragment (25) and has been suppressed in miRBase.”
miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades (2011, background): “In some invertebrates like sea squirt (37), but also to a lesser extent in mammals (38), particular miRNA precursor hairpins appear to undergo two rounds of Dicer cleavage, resulting in two miRNA duplexes being produced from each hairpin.”
MicroRNAs in stress signaling and human disease (2012, background): “However, since these additional miRNAs tend to be poorly conserved and expressed at low levels, their functional significance is unclear (Chiang et al., 2010; Landgraf et al., 2007).”
Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing (2010, methodology): “Out of 223 miRNA genomic loci producing 197 mouse miRNAs conserved in other mammals (Friedman et al., 2009), 203 miRNA loci producing miRNAs with 5’ ends validated from a large scale profiling of mouse miRNAs (Chiang et al. 2010) were used in the analysis of Figure 1A.”
An optimized microRNA backbone for effective single-copy RNAi. (2013, background): “Although many key players in miRNA biogenesis are known, our understanding of substrate RNA sequence features required for effective pri- and pre-miRNA processing is still limited (Chiang et al., 2010), hampering the rational optimization of shRNAmir backbones.”
Establishing the role of ATP for the function of the RIG-I innate immune sensor (2015, background): “Endogenous RNAs, such as tRNAs, inverted repeat sequence elements, and pre-and mature miRNAs, are abundant in the cytoplasm and contain structured duplex regions to which RIG-I can readily bind (Athanasiadis et al., 2004; Wang and Carmichael, 2004; Watanabe et al., 2008; Wang and Leung, 2009; Chiang”