The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans

Cell. 2002 Jun 28;109(7):861-71. doi: 10.1016/s0092-8674(02)00793-6.

Abstract

Double-stranded (ds) RNA induces potent gene silencing, termed RNA interference (RNAi). At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs). DCR-1 is also required for processing endogenous regulatory RNAs called miRNAs, but how DCR-1 recognizes its endogenous and foreign substrates is not yet understood. Here we show that the C. elegans RNAi pathway gene, rde-4, encodes a dsRNA binding protein that interacts during RNAi with RNA identical to the trigger dsRNA. RDE-4 protein also interacts in vivo with DCR-1, RDE-1, and a conserved DExH-box helicase. Our findings suggest a model in which RDE-4 and RDE-1 function together to detect and retain foreign dsRNA and to present this dsRNA to DCR-1 for processing.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cloning, Molecular
  • Conserved Sequence
  • DEAD-box RNA Helicases
  • Endoribonucleases / metabolism*
  • Gene Silencing
  • Helminth Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Peptide Mapping
  • Protein Binding
  • RNA Helicases / chemistry*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III
  • Sequence Homology, Amino Acid

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • RDE-4 protein, C elegans
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA-Binding Proteins
  • rde-1 protein, C elegans
  • DRH-1 protein, C elegans
  • DRH-2 protein, C elegans
  • Endoribonucleases
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • RNA Helicases

Associated data

  • GENBANK/AF480439
  • GENBANK/AF480440
  • GENBANK/AY071926