RRC ID |
46742
|
Author |
Vasale JJ, Gu W, Thivierge C, Batista PJ, Claycomb JM, Youngman EM, Duchaine TF, Mello CC, Conte D Jr.
|
Title |
Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway.
|
Journal |
Proc Natl Acad Sci U S A
|
Abstract |
Argonaute (AGO) proteins interact with distinct classes of small RNAs to direct multiple regulatory outcomes. In many organisms, including plants, fungi, and nematodes, cellular RNA-dependent RNA polymerases (RdRPs) use AGO targets as templates for amplification of silencing signals. Here, we show that distinct RdRPs function sequentially to produce small RNAs that target endogenous loci in Caenorhabditis elegans. We show that DCR-1, the RdRP RRF-3, and the dsRNA-binding protein RDE-4 are required for the biogenesis of 26-nt small RNAs with a 5' guanine (26G-RNAs) and that 26G-RNAs engage the Piwi-clade AGO, ERGO-1. Our findings support a model in which targeting by ERGO-1 recruits a second RdRP (RRF-1 or EGO-1), which in turn transcribes 22G-RNAs that interact with worm-specific AGOs (WAGOs) to direct gene silencing. ERGO-1 targets exhibit a nonrandom distribution in the genome and appear to include many gene duplications, suggesting that this pathway may control overexpression resulting from gene expansion.
|
Volume |
107(8)
|
Pages |
3582-7
|
Published |
2010-2-23
|
DOI |
10.1073/pnas.0911908107
|
PII |
0911908107
|
PMID |
20133583
|
PMC |
PMC2840456
|
MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Endoribonucleases / metabolism
Gene Silencing
RNA Interference*
RNA, Small Interfering / biosynthesis*
RNA, Small Interfering / genetics
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
RNA-Dependent RNA Polymerase / metabolism*
Ribonuclease III
Transcription, Genetic
|
IF |
9.412
|
Times Cited |
94
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
C.elegans |
tm894
tm914
tm1120
tm1637
tm887
tm1019
tm1144
tm1860
tm1195 |