The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans.
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.
Program in Molecular Medicine, University of Massachusetts Meidcal School, Worcester, MA 1605, USA.
Hiroaki
H
Tabara
Erbay
E
Yigit
Haruhiko
H
Siomi
Craig C
CC
Mello
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases; D004722:Endoribonucleases / Q000378:metabolism*; D020868:Gene Silencing; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011485:Protein Binding; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C461645:RDE-4 protein, C elegans; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C122185:rde-1 protein, C elegans; C461646:DRH-1 protein, C elegans; C461647:DRH-2 protein, C elegans; D004722:Endoribonucleases; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases