The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis.
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.
['Deffit|Sarah N|SN|', 'Yee|Brian A|BA|', 'Manning|Aidan C|AC|', 'Rajendren|Suba|S|', 'Vadlamani|Pranathi|P|', 'Wheeler|Emily C|EC|', 'Domissy|Alain|A|', 'Washburn|Michael C|MC|', 'Yeo|Gene W|GW|', 'Hundley|Heather A|HA|http://orcid.org/0000-0002-9106-9016']
D000241:Adenosine D000243:Adenosine Deaminase D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D002633:Chemotaxis D020869:Gene Expression Profiling D005786:Gene Expression Regulation D007288:Inosine D012333:RNA, Messenger
C. elegans ADAR gene expression genes inosine RNA editing RNA biology chromosomes evolutionary biology genomics post-transcriptional gene regulation