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 Hundley

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article numbere28625
JournaleLife
Volume6
DOIs
StatePublished - Sep 19 2017

Fingerprint

Caenorhabditis elegans
Chemotaxis
Gene expression
Transcriptome
Gene Expression
Messenger RNA
RNA Editing
Phenotype
Inosine
Deamination
Adenosine
Animals
Software
RNA
Defects
Enzymes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Deffit, S. N., Yee, B. A., Manning, A. C., Rajendren, S., Vadlamani, P., Wheeler, E. C., ... Hundley, H. (2017). The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis. eLife, 6, [e28625]. https://doi.org/10.7554/eLife.28625

The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis. / Deffit, Sarah N.; Yee, Brian A.; Manning, Aidan C.; Rajendren, Suba; Vadlamani, Pranathi; Wheeler, Emily C.; Domissy, Alain; Washburn, Michael C.; Yeo, Gene W.; Hundley, Heather.

In: eLife, Vol. 6, e28625, 19.09.2017.

Research output: Contribution to journalArticle

Deffit, SN, Yee, BA, Manning, AC, Rajendren, S, Vadlamani, P, Wheeler, EC, Domissy, A, Washburn, MC, Yeo, GW & Hundley, H 2017, 'The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis', eLife, vol. 6, e28625. https://doi.org/10.7554/eLife.28625
Deffit SN, Yee BA, Manning AC, Rajendren S, Vadlamani P, Wheeler EC et al. The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis. eLife. 2017 Sep 19;6. e28625. https://doi.org/10.7554/eLife.28625
Deffit, Sarah N. ; Yee, Brian A. ; Manning, Aidan C. ; Rajendren, Suba ; Vadlamani, Pranathi ; Wheeler, Emily C. ; Domissy, Alain ; Washburn, Michael C. ; Yeo, Gene W. ; Hundley, Heather. / The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis. In: eLife. 2017 ; Vol. 6.
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