title: Genetic mapping uncovers cis-regulatory landscape of RNA editing.
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.
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Gokul
authors.initials: G
authors.lastname: Ramaswami
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Deng
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Anna Carbone
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Trudy F C
authors.initials: TFC
authors.lastname: Mackay
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Billy Li
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D002874:Chromosome Mapping; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D040641:Quantitative Trait Loci; D017393:RNA Editing; D012330:RNA, Double-Stranded / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid
chemical_list: D029721:Drosophila Proteins; D012330:RNA, Double-Stranded; D038621:Regulatory Sequences, Ribonucleic Acid; C567956:Adar protein, Drosophila; D000243:Adenosine Deaminase