Adenosine deaminases that act on RNA induce reproducible changes in abundance and sequence of embryonic miRNAs
- Cornelia Vesely1,4,
- Stefanie Tauber2,3,4,
- Fritz J. Sedlazeck2,3,
- Arndt von Haeseler2,3 and
- Michael F. Jantsch1,5
- 1Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria;
- 2Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, A-1030 Vienna, Austria;
- 3University of Veterinary Medicine, A-1030 Vienna, Austria
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↵4 These authors contributed equally to this work.
Abstract
Adenosine deaminases that act on RNA bind double-stranded and structured RNAs and convert adenosines to inosines by hydrolytic deamination. Inosines are recognized as guanosines, and, hence, RNA editing alters the sequence information but also structure of RNAs. Editing by ADARs is widespread and essential for normal life and development. Precursors of miRNAs are abundantly edited by ADARs, but neither the abundance nor the consequences of miRNA editing has been firmly established. Using transgenic mouse embryos that are deficient in the two enzymatically active editing enzymes ADAR and ADARB1, we compare relative frequencies but also sequence composition of miRNAs in these genetically modified backgrounds to wild-type mice by “next-generation sequencing.” Deficiency of ADARB1 leads to a reproducible change in abundance of specific miRNAs and their predicted targets. Changes in miRNA abundance seem unrelated to editing events. Additional deletion of ADAR has surprisingly little impact on the mature miRNA repertoire, indicating that miRNA expression is primarily dependent on ADARB1. A-to-G transitions reflecting A-to-I editing events can be detected at few sites and at low frequency during the early embryonic stage investigated. Again, most editing events are ADARB1-dependent with only few editing sites being specifically edited by ADAR. Besides known editing events in miRNAs, a few novel, previously unknown editing events were identified. Some editing events are located to the seed region of miRNAs, opening the possibility that editing leads to their retargeting.
Footnotes
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↵5 Corresponding author
E-mail Michael.Jantsch{at}univie.ac.at
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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.133025.111.
Freely available online through the Genome Research Open Access option.
- Received October 6, 2011.
- Accepted February 1, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
