The role of RNA editing by ADARs in RNAi

Mol Cell. 2002 Oct;10(4):809-17. doi: 10.1016/s1097-2765(02)00649-4.

Abstract

Adenosine deaminases that act on RNA (ADARs) are RNA-editing enzymes that deaminate adenosines to create inosines in double-stranded RNA (dsRNA). Here we demonstrate that ADARs are not required for RNA interference (RNAi) and that they do not antagonize the pathway to a detectable level when RNAi is initiated by injecting dsRNA. We find, however, that transgenes expressed in the somatic tissues of wild-type animals are silenced in strains with deletions in the two genes encoding ADARs, adr-1 and adr-2. Transgene-induced gene silencing in adr-1;adr-2 mutants depends on genes required for RNAi, suggesting that a dsRNA intermediate is involved. In wild-type animals we detect edited dsRNA corresponding to transgenes, and we propose that editing of this dsRNA prevents somatic transgenes from initiating RNAi in wild-type animals.

Publication types

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

MeSH terms

  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Calmodulin-Binding Proteins / genetics
  • Gene Deletion
  • Gene Silencing
  • Genotype
  • Heat-Shock Proteins / genetics
  • Muscle Proteins / genetics
  • Neurons / enzymology
  • Neurons / metabolism
  • RNA Editing*
  • RNA Interference* / drug effects
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transgenes / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Calmodulin-Binding Proteins
  • Heat-Shock Proteins
  • Muscle Proteins
  • RNA, Double-Stranded
  • unc-22 protein, C elegans
  • Adenosine Deaminase