Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage

Cattenoz, Pierre B., Taft, Ryan J., Westhof, Eric and Mattick, John S. (2013) Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage. RNA, 19 2: 257-270. doi:10.1261/rna.036202.112

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Author Cattenoz, Pierre B.
Taft, Ryan J.
Westhof, Eric
Mattick, John S.
Title Transcriptome-wide identification of A > I RNA editing sites by inosine specific cleavage
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1261/rna.036202.112
Open Access Status File (Publisher version)
Volume 19
Issue 2
Start page 257
End page 270
Total pages 14
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
Abstract Adenosine to inosine (A > I) RNA editing, which is catalyzed by the ADAR family of proteins, is one of the fundamental mechanisms by which transcriptomic diversity is generated. Indeed, a number of genome-wide analyses have shown that A > I editing is not limited to a few mRNAs, as originally thought, but occurs widely across the transcriptome, especially in the brain. Importantly, there is increasing evidence that A > I editing is essential for animal development and nervous system function. To more efficiently characterize the complete catalog of ADAR events in the mammalian transcriptome we developed a high-throughput protocol to identify A > I editing sites, which exploits the capacity of glyoxal to protect guanosine, but not inosine, from RNAse T1 treatment, thus facilitating extraction of RNA fragments with inosine bases at their termini for high-throughput sequencing. Using this method we identified 665 editing sites in mouse brain RNA, including most known sites and suite of novel sites that include nonsynonymous changes to protein-coding genes, hyperediting of genes known to regulate p53, and alterations to non-protein-coding RNAs. This method is applicable to any biological system for the de novo discovery of A > I editing sites, and avoids the complicated informatic and practical issues associated with editing site identification using traditional RNA sequencing data. This approach has the potential to substantially increase our understanding of the extent and function of RNA editing, and thereby to shed light on the role of transcriptional plasticity in evolution, development, and cognition.
Keyword ADAR
Noncoding RNA
Ion channel
Deep sequencing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published in Advance December 21, 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Thu, 17 Jan 2013, 12:03:59 EST by Susan Allen on behalf of Institute for Molecular Bioscience