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Nucleic Acids Res. 2014 Oct 29;42(19):12155-68. doi: 10.1093/nar/gku844. Epub 2014 Sep 26.

ADAR2 induces reproducible changes in sequence and abundance of mature microRNAs in the mouse brain.

Author information

  • 1Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9, A-1030 Vienna, Austria.
  • 2Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, and University of Veterinary Medicine, Dr. Bohr Gasse 9, A-1030 Vienna, Austria.
  • 3Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, and University of Veterinary Medicine, Dr. Bohr Gasse 9, A-1030 Vienna, Austria Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, Währinger Straße 29, A-1090 Vienna, Austria.
  • 4Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9, A-1030 Vienna, Austria michael.jantsch@univie.ac.at.

Abstract

Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded RNAs including miRNA precursors. A to I editing is widespread and required for normal life. By comparing deep sequencing data of brain miRNAs from wild-type and ADAR2 deficient mouse strains, we detect editing sites and altered miRNA processing at high sensitivity. We detect 48 novel editing events in miRNAs. Some editing events reach frequencies of up to 80%. About half of all editing events depend on ADAR2 while some miRNAs are preferentially edited by ADAR1. Sixty-four percent of all editing events are located within the seed region of mature miRNAs. For the highly edited miR-3099, we experimentally prove retargeting of the edited miRNA to novel 3' UTRs. We show further that an abundant editing event in miR-497 promotes processing by Drosha of the corresponding pri-miRNA. We also detect reproducible changes in the abundance of specific miRNAs in ADAR2-deficient mice that occur independent of adjacent A to I editing events. This indicates that ADAR2 binding but not editing of miRNA precursors may influence their processing. Correlating with changes in miRNA abundance we find misregulation of putative targets of these miRNAs in the presence or absence of ADAR2.

PMID:
25260591
PMCID:
PMC4231736
DOI:
10.1093/nar/gku844
[PubMed - indexed for MEDLINE]
Free PMC Article
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