ADARs mediate distinct RNA editing activity and gene regulation in the Caenorhabditis elegans germline

Abstract

Tissues rely on unique landscapes of gene regulation to allow the organism to correctly develop, function, and respond to changes. One component of these gene regulatory networks is RNA Binding Proteins (RBPs) which bind and modify RNA molecules leading to changes in the cellular fate of transcripts. The Adenosine DeAminase acting on RNA (ADAR) family of RBPs modify RNAs by catalyzing the deamination of adenosine (A) to inosine (I), known as A-to-I RNA editing. Prompted by recent evidence that ADARs play important roles in germline biology, we profiled editing activity of the A-to-I editing enzyme ADR-2 on transcripts in the Caenorhabditis elegans germline. These analyses revealed that many germline editing events are distinct from editing events in other tissues; however, the previously described role of the inactive deaminase ADR-1 in regulating editing activity by ADR-2 is conserved in the germline. We find that complete loss or misregulation of editing has little effect on the expression of edited transcripts within the germline; however, loss of ADARs results in the misexpression of several unedited germline transcripts. Intriguingly, further investigation reveals that these expression changes are buffered at the translational level. In all, the results of this study suggest that ADARs show unique activity in the C. elegans germline and that compensatory mechanisms exist to lessen the immediate consequences of loss of ADAR function within the germline.