Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi

Nat Struct Mol Biol. 2011 Dec 18;19(1):90-7. doi: 10.1038/nsmb.2186.

Abstract

Endogenous RNA interference (endo-RNAi) pathways use a variety of mechanisms to generate siRNA and to mediate gene silencing. In Caenorhabditis elegans, DCR-1 is essential for competing RNAi pathways-the ERI endo-RNAi pathway and the exogenous RNAi pathway-to function. Here, we demonstrate that DCR-1 forms exclusive complexes in each pathway and further define the ERI-DCR-1 complex. We show that the tandem tudor protein ERI-5 potentiates ERI endo-RNAi by tethering an RNA-dependent RNA polymerase (RdRP) module to DCR-1. In the absence of ERI-5, the RdRP module is uncoupled from DCR-1. Notably, EKL-1, an ERI-5 paralog that specifies distinct RdRP modules in Dicer-independent endo-RNAi pathways, partially compensates for the loss of ERI-5 without interacting with DCR-1. Our results implicate tudor proteins in the recruitment of RdRP complexes to specific steps within DCR-1-dependent and DCR-1-independent endo-RNAi pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Immunoprecipitation
  • Mutation
  • Protein Binding
  • RNA Interference*
  • RNA Replicase / genetics
  • RNA Replicase / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Recombinant Proteins / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • ERI-5 protein, C elegans
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • Recombinant Proteins
  • RNA Replicase
  • dcr-1 protein, C elegans
  • Ribonuclease III