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Published online before print
November 7, 2007, 10.1101/gr.6593807 Genome Res. 17:1865-1879, 2007 ©2007 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/07 $5.00 OPEN ACCESS ARTICLE
12 Drosophila Genomes/Letter Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes1 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA; 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3 Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA
MicroRNAs (miRNAs) are short regulatory RNAs that inhibit target genes by complementary binding in 3' untranslated regions (3' UTRs). They are one of the most abundant classes of regulators, targeting a large fraction of all genes, making their comprehensive study a requirement for understanding regulation and development. Here we use 12 Drosophila genomes to define structural and evolutionary signatures of miRNA hairpins, which we use for their de novo discovery. We predict >41 novel miRNA genes, which encompass many unique families, and 28 of which are validated experimentally. We also define signals for the precise start position of mature miRNAs, which suggest corrections of previously known miRNAs, often leading to drastic changes in their predicted target spectrum. We show that miRNA discovery power scales with the number and divergence of species compared, suggesting that such approaches can be successful in human as dozens of mammalian genomes become available. Interestingly, for some miRNAs sense and anti-sense hairpins score highly and mature miRNAs from both strands can indeed be found in vivo. Similarly, miRNAs with weak 5' end predictions show increased in vivo processing of multiple alternate 5' ends and have fewer predicted targets. Lastly, we show that several miRNA star sequences score highly and are likely functional. For mir-10 in particular, both arms show abundant processing, and both show highly conserved target sites in Hox genes, suggesting a possible cooperation of the two arms, and their role as a master Hox regulator.
4 These authors contributed equally to this work. 5 Present address: Institute of Computer Science, University of Tartu, Estonia and Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. E-mail manoli{at}mit.edu; fax (617) 253-6652. E-mail alex.stark{at}mit.edu; fax (617) 253-6652. [Supplemental material is available online at www.genome.org. All data and predictions are available at http://compbio.mit.edu/fly/mirnas/.] Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6593807
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