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PMID: 26373807 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Genetic mapping uncovers cis-regulatory landscape of RNA editing.

Nature communications ·Vol. 6 ·2015-09-16 ·Pages 8194

Ramaswami G, Deng P, Zhang R, Anna Carbone M, Mackay TFC, Billy Li J

Abstract

Adenosine-to-inosine (A-to-I) RNA editing, catalysed by ADAR enzymes conserved in metazoans, plays an important role in neurological functions. Although the fine-tuning mechanism provided by A-to-I RNA editing is important, the underlying rules governing ADAR substrate recognition are not well understood. We apply a quantitative trait loci (QTL) mapping approach to identify genetic variants associated with variability in RNA editing. With very accurate measurement of RNA editing levels at 789 sites in 131 Drosophila melanogaster strains, here we identify 545 editing QTLs (edQTLs) associated with differences in RNA editing. We demonstrate that many edQTLs can act through changes in the local secondary structure for edited dsRNAs. Furthermore, we find that edQTLs located outside of the edited dsRNA duplex are enriched in secondary structure, suggesting that distal dsRNA structure beyond the editing site duplex affects RNA editing efficiency. Our work will facilitate the understanding of the cis-regulatory code of RNA editing.

MeSH Terms
Adenosine Deaminase/metabolism Animals Chromosome Mapping Drosophila Proteins/metabolism Drosophila melanogaster Quantitative Trait Loci RNA Editing RNA, Double-Stranded/metabolism Regulatory Sequences, Ribonucleic Acid
Chemicals
Drosophila Proteins RNA, Double-Stranded Regulatory Sequences, Ribonucleic Acid Adar protein, Drosophila Adenosine Deaminase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ramaswami Gokul
Department of Genetics, Stanford University, Stanford, California 94305, USA.
Deng Patricia
Department of Genetics, Stanford University, Stanford, California 94305, USA.
Zhang Rui
Department of Genetics, Stanford University, Stanford, California 94305, USA.
Anna Carbone Mary
Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
Mackay Trudy F C
Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
Billy Li Jin
Department of Genetics, Stanford University, Stanford, California 94305, USA.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms9194
Published
2015-09-16
Epub
2015-00-16
Pages
8194
Language
English
Region
England
NLM ID
101528555
PMCID
PMC4573499
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007276 · United States
NIGMS NIH HHS · R01 GM045146 · United States
NHGRI NIH HHS · T32 HG000044 · United States
NIGMS NIH HHS · R01 GM102484 · United States
NIGMS NIH HHS · GM45146 · United States
Databases
GEO
GSE67082
External Links
PubMed source DOI: 10.1038/ncomms9194 PMC Full Text View journal details
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