RRC ID 4338
Author Duchaine TF, Wohlschlegel JA, Kennedy S, Bei Y, Conte D Jr, Pang K, Brownell DR, Harding S, Mitani S, Ruvkun G, Yates JR 3rd, Mello CC.
Title Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways.
Journal Cell
Abstract In plants, animals, and fungi, members of the Dicer family of RNase III-related enzymes process double-stranded RNA (dsRNA) to initiate small-RNA-mediated gene-silencing mechanisms. To learn how C. elegans Dicer, DCR-1, functions in multiple distinct silencing mechanisms, we used a mass-spectrometry-based proteomics approach to identify DCR-1-interacting proteins. We then generated and characterized deletion alleles for the corresponding genes. The interactors are required for production of three species of small RNA, including (1) small interfering RNAs (siRNAs), derived from exogenous dsRNA triggers (exo-siRNAs); (2) siRNAs derived from endogenous triggers (endo-siRNAs); and (3) developmental regulatory microRNAs (miRNAs). One interactor, the conserved RNA-phosphatase homolog PIR-1, is required for the processing of a putative amplified DCR-1 substrate. Interactors required for endo-siRNA production include ERI-1 and RRF-3, whose loss of function enhances RNAi. Our findings provide a first glimpse at the complex biochemical niche of Dicer and suggest that competition exists between DCR-1-mediated small-RNA pathways.
Volume 124(2)
Pages 343-54
Published 2006-1-27
DOI 10.1016/j.cell.2005.11.036
PII S0092-8674(05)01394-2
PMID 16439208
MeSH Amino Acid Sequence Animals Binding, Competitive Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Endoribonucleases / genetics* Endoribonucleases / metabolism Exoribonucleases / genetics Exoribonucleases / metabolism Gene Deletion Mass Spectrometry MicroRNAs / metabolism* Models, Biological Molecular Sequence Data Molecular Structure Proteomics RNA Interference RNA Replicase / genetics RNA Replicase / metabolism RNA, Small Interfering / metabolism* Ribonuclease III Sequence Alignment Signal Transduction / genetics*
IF 38.637
Times Cited 267
C.elegans tm1496 tm1217 tm1361 tm1705