@article{ff3dba3b38194da59f39e36e0d9718dd,
title = "Distinct Argonaute-Mediated 22G-RNA Pathways Direct Genome Surveillance in the C. elegans Germline",
abstract = "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.",
keywords = "DNA, RNA",
author = "Weifeng Gu and Masaki Shirayama and Darryl Conte and Jessica Vasale and Batista, {Pedro J.} and Claycomb, {Julie M.} and Moresco, {James J.} and Youngman, {Elaine M.} and Jennifer Keys and Stoltz, {Matthew J.} and Chen, {Chun Chieh G.} and Chaves, {Daniel A.} and Shenghua Duan and Kasschau, {Kristin D.} and Noah Fahlgren and Yates, {John R.} and Shohei Mitani and Carrington, {James C.} and Mello, {Craig C.}",
note = "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Illumina sequencing, J. Priess for providing RFP::PGL-1, M. Hammell for help with statistics, R. Ketting for sharing unpublished data, and the CGC for providing strains.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 Funda{\c c}{\~a}o para Ci{\^e}ncia 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. ",
year = "2009",
month = oct,
day = "23",
doi = "10.1016/j.molcel.2009.09.020",
language = "English (US)",
volume = "36",
pages = "231--244",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}