| 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, Small Interfering / metabolism*
RNA-Dependent RNA Polymerase / genetics
RNA-Dependent RNA Polymerase / metabolism
Ribonuclease III
Sequence Alignment
Signal Transduction / genetics*
|
| IF |
38.637
|
| Times Cited |
267
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1496
tm1217
tm1361
tm1705 |