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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cloning, Molecular
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Conserved Sequence
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DEAD-box RNA Helicases
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Endoribonucleases / metabolism*
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Gene Silencing
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Helminth Proteins / metabolism*
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Humans
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Molecular Sequence Data
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Peptide Mapping
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Protein Binding
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RNA Helicases / chemistry*
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RNA Helicases / genetics
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RNA Helicases / metabolism*
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Ribonuclease III
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Sequence Homology, Amino Acid
Substances
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Caenorhabditis elegans Proteins
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Helminth Proteins
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RDE-4 protein, C elegans
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RNA, Double-Stranded
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RNA, Messenger
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RNA-Binding Proteins
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rde-1 protein, C elegans
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DRH-1 protein, C elegans
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DRH-2 protein, C elegans
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Endoribonucleases
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Ribonuclease III
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DEAD-box RNA Helicases
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RNA Helicases
Associated data
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GENBANK/AF480439
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GENBANK/AF480440
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GENBANK/AY071926