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