Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs.

By J. Ruby, Alexander Stark, W. K. Johnston, Manolis Kellis, David P. Bartel, Eric C. Lai. Genome Research, 2007

637 citations recorded by the source corpus.

MicroRNA (miRNA) genes give rise to small regulatory RNAs in a wide variety of organisms. We used computational methods to predict miRNAs conserved among Drosophila species and large-scale sequencing of small RNAs from Drosophila melanogaster to experimentally confirm and complement these predictions. In addition to validating 20 of our top 45 predictions for novel miRNA loci, the large-scale sequencing identified many miRNAs that had not been predicted. In total, 59 novel genes were identified, increasing our tally of confirmed fly miRNAs to 148. The large-scale sequencing also refined the identities of previously known miRNAs and provided insights into their biogenesis and expression. Many miRNAs were expressed in particular developmental contexts, with a large cohort of miRNAs expressed primarily in imaginal discs. Conserved miRNAs typically were expressed more broadly and robustly than were nonconserved miRNAs, and those conserved miRNAs with more restricted expression tended to have fewer predicted targets than those expressed more broadly. Predicted targets for the expanded set of microRNAs substantially increased and revised the miRNA-target relationships that appear conserved among the fly species. Insights were also provided into miRNA gene evolution, including evidence for emergent regulatory function deriving from the opposite arm of the miRNA hairpin, exemplified by mir-10, and even the opposite strand of the DNA, exemplified by mir-iab-4.

Subfields: Cancer Research, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/675a509e10651c99d595e678fc3b96353ab8c565

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Citations in the corpus

Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs (2011, background): “, and highly or broadly expressed miRNAs seem to target more mRNAs than do other”
Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. (2008, methodology): “Classification of small RNAs based on processing dependencies Small RNAs collected from wild-type, dgcr8 / , and dicer1 / mESCs were sequenced using the Illumina and 454 high-throughput sequencing technologies (Seo et al. 2004; Margulies et al. 2005).”
Metazoan MicroRNAs (2018, background): “These RNAs that are both pre-miRNAs and introns are called “mirtrons” (Ruby et al., 2007a).”
Evolution of microRNA diversity and regulation in animals (2011, background): “Gene duplication events, followed by subfunctionalization and neofunctionalization processe”
miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades (2011, background): “Since the ﬂy data has already been mined for miRNAs (44) we speculate that few yet remain in the data to be detected.”
Genomewide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation (2014, positive): “We typically consider miRNAs that are conserved throughout Sophophora to be well conserved and cataloged 2-8 or 6merA seed matches to such miRNAs (Ruby et al., 2007).”
Biological principles of microRNA-mediated regulation: shared themes amid diversity (2008, background): “Target predictions based primarily on conserved seed pairing and local sequence or structural features suggest that individual animal miRNAs often have >100 targets, and that at least 20–30% of animal transcripts bear one or more conserved miRNA binding sites in their 3′ UT”
Most mammalian mRNAs are conserved targets of microRNAs. (2008, methodology): “2B; Brennecke et al. 2005; Grun et al. 2005; Krek et al. 2005; Lewis et al. 2005; Lall et al. 2006; Ruby et al. 2006, 2007; Gaidatzis et al. 2007).”
Mammalian mirtron genes. (2007, background): “Consistent with this, while several mirtrons are highly conserved among Drosophilids (Okamura et al., 2007; Ruby et al., 2007a), nematodes (Ruby et al., 2007a), and mammals (this work), these animals do not collectively share any mirtrons that are clearly related by ancestry.”
Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. (2010, methodology): “Indeed, recent work in invertebrates and plants (Rajagopalan et al. 2006; Ruby et al. 2006, 2007b) has shown that the fraction of erroneously annotated miRNAs can be quite high, depending on the quality of the initial computational predictions.”
Small silencing RNAs: an expanding universe (2009, neutral): “5 million distinct piRNAs identified thus far in flies, but collectively they map to a few hundred genomic cluster”
An endogenous small interfering RNA pathway in Drosophila (2008, background): “published sequences derived from 19–26-nucleotide RNAs from S2 cells 15 .”
Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq (2013, positive): “A similar result was obtained for regions that contained at least 5 poly-‐adenylation motifs (AATAAA) or 3 seed sites for the microRNAs bantam, miR-‐14, miR-‐34, miR-‐2a, or miR-‐2b, which are all highly ”