RRC ID 46233
Author Washburn MC, Kakaradov B, Sundararaman B, Wheeler E, Hoon S, Yeo GW, Hundley HA.
Title The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.
Journal Cell Rep
Abstract Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need to study deaminase-independent control of editing. C. elegans have two ADAR proteins, ADR-2 and the theoretically catalytically inactive ADR-1. Using high-throughput RNA sequencing of wild-type and adr mutant worms, we expand the repertoire of C. elegans edited transcripts over 5-fold and confirm that ADR-2 is the only active deaminase in vivo. Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3' UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2, and mutations within its double-stranded RNA (dsRNA) binding domains abolish both binding and editing regulation. We conclude that ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo. These results raise the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing through deaminase-independent mechanisms.
Volume 6(4)
Pages 599-607
Published 2014-2-27
DOI 10.1016/j.celrep.2014.01.011
PII S2211-1247(14)00028-X
PMID 24508457
PMC PMC3959997
MeSH 3' Untranslated Regions Adenosine / genetics Adenosine / metabolism Adenosine Deaminase / genetics Adenosine Deaminase / metabolism* Animals Binding Sites Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Inosine / genetics Inosine / metabolism Mutation Protein Binding RNA Editing* RNA, Double-Stranded / chemistry RNA, Double-Stranded / metabolism* Transcriptome*
IF 7.815
Times Cited 32
C.elegans tm668