Systematic identification of edited microRNAs in the human brain
- Shahar Alon1,9,
- Eyal Mor2,9,
- Francois Vigneault3,4,5,9,
- George M. Church3,4,
- Franco Locatelli6,7,
- Federica Galeano6,
- Angela Gallo6,10,
- Noam Shomron2,10 and
- Eli Eisenberg8,10
- 1Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel;
- 2Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel;
- 3Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, USA;
- 5Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA;
- 6Oncohaematology Department, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome 00165, Italy;
- 7Università di Pavia, Pavia 27100, Italy;
- 8Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978, Israel
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↵9 These authors contributed equally to this work.
Abstract
Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread.
Footnotes
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↵10 Corresponding authors
E-mail elieis{at}post.tau.ac.il
E-mail nshomron{at}post.tau.ac.il
E-mail angela.gallo{at}opbg.net
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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.131573.111.
- Received September 6, 2011.
- Accepted April 4, 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/.
