Genetic mapping uncovers cis-regulatory landscape of RNA editing

Gokul Ramaswami, Patricia Deng, Rui Zhang, Mary Anna Carbone, Trudy F. C. Mackay and Jin Billy Li ()
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Gokul Ramaswami: Stanford University
Patricia Deng: Stanford University
Rui Zhang: Stanford University
Mary Anna Carbone: Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University
Trudy F. C. Mackay: Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University
Jin Billy Li: Stanford University

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9194

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