Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence
- Eugene Berezikov1,
- Nicolas Robine2,
- Anastasia Samsonova3,
- Jakub O. Westholm2,
- Ammar Naqvi2,
- Jui-Hung Hung4,8,
- Katsutomo Okamura2,
- Qi Dai2,
- Diane Bortolamiol-Becet2,
- Raquel Martin2,
- Yongjun Zhao5,
- Phillip D. Zamore6,
- Gregory J. Hannon7,
- Marco A. Marra5,
- Zhiping Weng8,
- Norbert Perrimon3 and
- Eric C. Lai2,9
- 1 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands;
- 2 Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065,USA;
- 3 Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4 Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA;
- 5 British Columbia Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada;
- 6 Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 7 Howard Hughes Medical Institute and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
- 8 Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
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.
Footnotes
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↵9 Corresponding author.
E-mail laie{at}mskcc.org; fax (212) 717-3604.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.116657.110.
- Received October 14, 2010.
- Accepted December 7, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.
