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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
eLife | 2017

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.

Pubmed ID: 28925356

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG004659
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008666
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM119257
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS075449

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