TY - JOUR
T1 - Distinct Argonaute-Mediated 22G-RNA Pathways Direct Genome Surveillance in the C. elegans Germline
AU - Gu, Weifeng
AU - Shirayama, Masaki
AU - Conte, Darryl
AU - Vasale, Jessica
AU - Batista, Pedro J.
AU - Claycomb, Julie M.
AU - Moresco, James J.
AU - Youngman, Elaine M.
AU - Keys, Jennifer
AU - Stoltz, Matthew J.
AU - Chen, Chun Chieh G.
AU - Chaves, Daniel A.
AU - Duan, Shenghua
AU - Kasschau, Kristin D.
AU - Fahlgren, Noah
AU - Yates, John R.
AU - Mitani, Shohei
AU - Carrington, James C.
AU - Mello, Craig C.
N1 - Funding Information:
We thank E. Kittler and UMass Deep Sequencing Core facility for Illumina sequencing, J. Priess for providing RFP::PGL-1, M. Hammell for help with statistics, R. Ketting for sharing unpublished data, and the CGC for providing strains. P.J.B. and D.A.C. were supported by SFRH/BD/11803/2003 (P.J.B.) and SFRH/BD/17629/2004/H6BM (D.A.C.) from Fundação para Ciência e Tecnologia (Lisboa, Portugal). J.M.C. was an HHMI fellow of the LSRF. J.J.M. is supported by NIH grant DK074798. E.Y. is a Damon Runyon Fellow supported by the DRCRF (DRG-1983-08). J.R.Y. is supported by R41 RR011823 from the Yeast Resource Center. C.C.M. is a Howard Hughes Medical Institute Investigator. This work was supported in part by Ruth L. Kirschstein N.R.S.A. GM63348 (D.C.) and R01 grant GM58800 (C.C.M.) from the NIGMS. J.C.C. is supported by NSF grant MCB-0618433.
PY - 2009/10/23
Y1 - 2009/10/23
N2 - Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.
AB - Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.
KW - DNA
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=70349476898&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2009.09.020
DO - 10.1016/j.molcel.2009.09.020
M3 - Article
C2 - 19800275
AN - SCOPUS:70349476898
SN - 1097-2765
VL - 36
SP - 231
EP - 244
JO - Molecular cell
JF - Molecular cell
IS - 2
ER -