1. Chromosomes and Gene Expression
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The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis

  1. Sarah N Deffit
  2. Brian A Yee
  3. Aidan C Manning
  4. Suba Rajendren
  5. Pranathi Vadlamani
  6. Emily C Wheeler
  7. Alain Domissy
  8. Michael C Washburn
  9. Gene W Yeo  Is a corresponding author
  10. Heather A Hundley  Is a corresponding author
  1. Indiana University, United States
  2. University of California at San Diego, United States
  3. University of California, San Diego, United States
Research Article
  • Cited 19
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Cite this article as: eLife 2017;6:e28625 doi: 10.7554/eLife.28625

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.

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Author details

  1. Sarah N Deffit

    Medical Sciences Program, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Brian A Yee

    Department of Cellular and Molecular Medicine, Stem Cell Program, Institute for Genomic Medicine, University of California at San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Aidan C Manning

    Medical Sciences Program, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Suba Rajendren

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Pranathi Vadlamani

    Medical Sciences Program, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Emily C Wheeler

    Department of Cellular and Molecular Medicine, Stem Cell Program, Institute for Genomic Medicine, University of California at San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Alain Domissy

    Department of Cellular and Molecular Medicine, Stem Cell Program, Institute for Genomic Medicine, University of California at San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Michael C Washburn

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Gene W Yeo

    Department of Cellular and Molecular Medicine, Stem Cell Program, Institute for Genomic Medicine, University of California, San Diego, La Jolla, United States
    For correspondence
    geneyeo@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.

  10. Heather A Hundley

    Medical Sciences Program, Indiana University, Bloomington, United States
    For correspondence
    hahundle@indiana.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9106-9016

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

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: May 14, 2017
  2. Accepted: September 18, 2017
  3. Accepted Manuscript published: September 19, 2017 (version 1)
  4. Version of Record published: October 17, 2017 (version 2)
  5. Version of Record updated: October 23, 2017 (version 3)
  6. 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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