ADAR binding to dsRNA prevents exogenous RNAi from attacking self-produced dsRNA in C. elegans

Using Caenorhabditis elegans, we investigated the interplay between two host pathways that regulate dsRNA expression and function, A-to-I RNA editing by ADARs, and RNA interference (RNAi). We found that the number of siRNAs targeting edited genes is significantly upregulated in ADAR mutant animals.

In addition, despite an almost complete depletion of primary siRNAs generated from editing sites in wild-type animals, secondary siRNAs are generated from edited transcripts, suggesting that ADARs antagonize only the first step of RNAi processing. We show that ADARs interfere with the efficacy of exogenous RNAi in vivo, likely to prevent trans-silencing, and provide evidence that ADR-2 binding to dsRNA is required for efficient RNAi suppression.