Editing independent effects of ADARs on the miRNA/siRNA pathways

Abstract

Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR-B Q/R site. ADARs have also been shown to affect RNA interference (RNAi) and microRNA processing by deamination of specific adenosines to inosine. Here, we show that ADAR proteins can affect RNA processing independently of their enzymatic activity. We show that ADAR2 can modulate the processing of mir-376a2 independently of catalytic RNA editing activity. In addition, in a Drosophila assay for RNAi deaminase-inactive ADAR1 inhibits RNAi through the siRNA pathway. These results imply that ADAR1 and ADAR2 have biological functions as RNA-binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions.

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

“…Our data revealed that RNA editing has little correlation with mRNA expression changes in ADAR1 KD H9 cells (Supplementary information, Figure S4 and data not shown), which is in consistency with recent reports in other organisms [18][19][20]. We hypothesized that ADAR1 deficiency may lead to an altered miRNA repertoire, which in turn regulates mRNA expression in H9 cells and during differentiation.…”

“…Besides the catalytic activity of ADARs on miRNAs, it has been shown that ADARs can modulate the miR-NA/siRNA pathways independently of the editing activity in fly [19]. ADARs are also important for maintaining many small RNAs in C. elegans through both editing and non-editing activities [20].…”

Proteome diversification by adenosine to inosine RNA-editing

“…A recent study showed that catalytically inactive ADAR1 and ADAR2 can modulate the micro RNA and siRNA pathways in Drosophila. 32 Similar functions might be expected for the inactive ADAR homologues in mammals. Catalytically inactive proteins might influence alternative splicing, hnRNA packaging or mRNA transport by their ability to bind dsRNA.…”

ADAR-mediated RNA editing in non-coding RNA sequences

“…Drosha cleavage of pri-mR-376a2 was inhibited by catalytically inactive ADAR2 because of ADAR2 binding [103]. This result indicates that other dsRNA binding proteins may bind to the pri-miRNA or pre-miRNA hairpin structures and affect the miRNA processing.…”