The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome

Cell Rep. 2014 Feb 27;6(4):599-607. doi: 10.1016/j.celrep.2014.01.011. Epub 2014 Feb 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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*


  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • RNA, Double-Stranded
  • Inosine
  • Adenosine Deaminase
  • Adr-1 protein, C elegans
  • Adr-2 protein, C elegans
  • Adenosine

Associated data

  • GEO/GSE51556