title: R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway.
abstract: The RNA interference (RNAi) pathway is initiated by processing long double-stranded RNA into small interfering RNA (siRNA). The siRNA-generating enzyme was purified from Drosophila S2cells and consists of two stoichiometric subunits: Dicer-2(DCR-2) and a previously unknown protein that we named R2D2. R2D2 is homologous to the Caenorhabditis elegans RNAi protein RDE-4. Association with R2D2 does not affect the enzymatic activity of DCR-2. Rather, the DCR-2/R2D2 complex, but not DCR-2 alone, binds to siRNA and enhances sequence-specific messenger RNA degradation mediated by the RNA-initiated silencing complex (RISC). These results indicate that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D019921:Biotinylation; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D002460:Cell Line; D011232:Chemical Precipitation; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004722:Endoribonucleases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D043244:Ribonuclease III
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; C478068:R2D2 protein, Drosophila; C461645:RDE-4 protein, C elegans; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D011994:Recombinant Proteins; C478069:DCR-2 protein, Drosophila; D004722:Endoribonucleases; D043244:Ribonuclease III; D020365:RNA Helicases