The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis
Sarah N Deffit,
Brian A Yee,
Aidan C Manning,
Suba Rajendren,
Pranathi Vadlamani,
Emily C Wheeler,
Alain Domissy,
Michael C Washburn,
Gene W Yeo,
Heather A Hundley
Affiliations
Sarah N Deffit
Medical Sciences Program, Indiana University, Bloomington, Indiana
Brian A Yee
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States
Aidan C Manning
Medical Sciences Program, Indiana University, Bloomington, Indiana
Suba Rajendren
Department of Biology, Indiana University, Bloomington, Indiana
Pranathi Vadlamani
Medical Sciences Program, Indiana University, Bloomington, Indiana
Emily C Wheeler
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States
Alain Domissy
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States
Michael C Washburn
Department of Biology, Indiana University, Bloomington, Indiana
Gene W Yeo
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, San Diego, United States; Molecular Engineering Laboratory, Agency for Science, Technology and Research, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome. Development and implementation of publicly available software, SAILOR, identified 7361 A-to-I editing events across the neural transcriptome. Intersecting the neural editome with adr-2 associated gene expression changes, revealed an edited mRNA, clec-41, whose neural expression is dependent on deamination. Restoring clec-41 expression in adr-2 deficient neural cells rescued the chemotaxis defect, providing the first evidence that neuronal phenotypes of ADAR mutants can be caused by altered gene expression.
