Distinct Argonaute-Mediated 22G-RNA Pathways Direct Genome Surveillance in the C. elegans Germline

• Published in: Molecular cell Vol. 36; no. 2; pp. 231 - 244
• Main Authors: Gu, Weifeng, Shirayama, Masaki, Conte, Darryl, Vasale, Jessica, Batista, Pedro J., Claycomb, Julie M., Moresco, James J., Youngman, Elaine M., Keys, Jennifer, Stoltz, Matthew J., Chen, Chun-Chieh G., Chaves, Daniel A., Duan, Shenghua, Kasschau, Kristin D., Fahlgren, Noah, Yates, John R., Mitani, Shohei, Carrington, James C., Mello, Craig C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.10.2009
• Subjects: Alleles; Amino Acid Sequence; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - metabolism; DNA; DNA helicase; DNA-directed RNA polymerase; Gene silencing; Genome - genetics; Genomes; Germ Cells - metabolism; Granules; Models, Genetic; Molecular Sequence Data; Phylogeny; Protein Binding; Protein Structure, Tertiary; Pseudogenes; RNA; RNA Interference; RNA, Helminth - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; RNA-Dependent RNA Polymerase - metabolism; RNA-directed RNA polymerase; RNA-mediated interference; Sequence Analysis, RNA; Temperature; Transposons; RNA; DNA
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2009.09.020

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.