Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence

  1. Eric C. Lai8,9
  1. 1 Hubrecht Institute;
  2. 2 Sloan-Kettering Institute;
  3. 3 Harvard Medical School;
  4. 4 Boston University;
  5. 5 BC Genome Sciences Centre;
  6. 6 U Mass Worcester;
  7. 7 CSHL;
  8. 8 Memorial Sloan-Kettering Cancer Center
  1. * Corresponding author; email: laie{at}mskcc.org

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 datasets that we generated for the modENCODE project. In total, we began with >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 are 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.

  • Received October 14, 2010.
  • Accepted December 7, 2010.

This manuscript is Open Access.

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  1. Genome Res. gr.116657.110 Copyright © 2010, Cold Spring Harbor Laboratory Press

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