The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis
- Indiana University, United States
- University of California at San Diego, United States
- University of California, San Diego, United States
Abstract
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 7,361 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.
Article and author information
Author details
Funding
American Cancer Society (RSG-15-051-RMC)
- Heather A Hundley
Indiana Clinical and Translational Sciences Institute
- Sarah N Deffit
National Science Foundation
- Emily C Wheeler
National Institutes of Health (1F32GM119257-01A1)
- Sarah N Deffit
National Institutes of Health (T32GM00866)
- Emily C Wheeler
National Institutes of Health (HG004659)
- Gene W Yeo
National Institutes of Health (NS075449)
- Gene W Yeo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Version history
- Received: May 14, 2017
- Accepted: September 18, 2017
- Accepted Manuscript published: September 19, 2017 (version 1)
- Version of Record published: October 17, 2017 (version 2)
- Version of Record updated: October 23, 2017 (version 3)
- Version of Record updated: February 12, 2018 (version 4)
Copyright
© 2017, Deffit et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis
eLife 6:e28625.
https://doi.org/10.7554/eLife.28625
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