title: Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi.
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.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thivierge
authors.forename: Neetha
authors.initials: N
authors.lastname: Makil
authors.forename: Mathieu
authors.initials: M
authors.lastname: Flamand
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Vasale
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: Darryl
authors.initials: D
authors.lastname: Conte
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Duchaine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047468:Immunoprecipitation; D009154:Mutation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C570450:ERI-5 protein, C elegans; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D011994:Recombinant Proteins; D012324:RNA-Dependent RNA Polymerase; C118116:dcr-1 protein, C elegans; D043244:Ribonuclease III