title: Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence.
abstract: Since the initial annotation of miRNAs from cloned short RNAs by the Ambros, Tuschl, and Bartel groups in 2001, more than a hundred studies have sought to identify additional miRNAs in various species. We report here a meta-analysis of short RNA data from Drosophila melanogaster, aggregating published libraries with 76 data sets that we generated for the modENCODE project. In total, we began with more than 1 billion raw reads from 187 libraries comprising diverse developmental stages, specific tissue- and cell-types, mutant conditions, and/or Argonaute immunoprecipitations. We elucidated several features of known miRNA loci, including multiple phased byproducts of cropping and dicing, abundant alternative 5' termini of certain miRNAs, frequent 3' untemplated additions, and potential editing events. We also identified 49 novel genomic locations of miRNA production, and 61 additional candidate loci with limited evidence for miRNA biogenesis. Although these loci broaden the Drosophila miRNA catalog, this work supports the notion that a restricted set of cellular transcripts is competent to be specifically processed by the Drosha/Dicer-1 pathway. Unexpectedly, we detected miRNA production from coding and untranslated regions of mRNAs and found the phenomenon of miRNA production from the antisense strand of known loci to be common. Altogether, this study lays a comprehensive foundation for the study of miRNA diversity and evolution in a complex animal model.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
authors.forename: Nicolas
authors.initials: N
authors.lastname: Robine
authors.forename: Anastasia
authors.initials: A
authors.lastname: Samsonova
authors.forename: Jakub O
authors.initials: JO
authors.lastname: Westholm
authors.forename: Ammar
authors.initials: A
authors.lastname: Naqvi
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Hung
authors.forename: Katsutomo
authors.initials: K
authors.lastname: Okamura
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.forename: Diane
authors.initials: D
authors.lastname: Bortolamiol-Becet
authors.forename: Raquel
authors.initials: R
authors.lastname: Martin
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019295:Computational Biology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D017393:RNA Editing / Q000235:genetics; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D035683:MicroRNAs; D016372:RNA, Antisense; D012333:RNA, Messenger; D043244:Ribonuclease III