A-to-I editing of microRNAs in the mammalian brain increases during development
- 1Department of Molecular Biology & Functional Genomics, Stockholm University, SE-10691 Stockholm, Sweden;
- 2KTH Royal Institute of Technology, Science for Life Laboratory (SciLifeLab), Center for Industrial and Applied Mathematics (CIAM), School of Computer Science and Communication (CSC), SE-10044 Stockholm, Sweden
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↵3 These authors contributed equally to this work.
Abstract
Adenosine-to-inosine (A-to-I) RNA editing targets double-stranded RNA stem–loop structures in the mammalian brain. It has previously been shown that miRNAs are substrates for A-to-I editing. For the first time, we show that for several definitions of edited miRNA, the level of editing increases with development, thereby indicating a regulatory role for editing during brain maturation. We use high-throughput RNA sequencing to determine editing levels in mature miRNA, from the mouse transcriptome, and compare these with the levels of editing in pri-miRNA. We show that increased editing during development gradually changes the proportions of the two miR-376a isoforms, which previously have been shown to have different targets. Several other miRNAs that also are edited in the seed sequence show an increased level of editing through development. By comparing editing of pri-miRNA with editing and expression of the corresponding mature miRNA, we also show an editing-induced developmental regulation of miRNA expression. Taken together, our results imply that RNA editing influences the miRNA repertoire during brain maturation.
Footnotes
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↵4 Corresponding author
E-mail marie.ohman{at}molbio.su.se
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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.131912.111.
- Received September 13, 2011.
- Accepted May 22, 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/.
