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

Weifeng Gu, Masaki Shirayama, Darryl Conte, Jessica Vasale, Pedro J. Batista, Julie M. Claycomb, James J. Moresco, Elaine M. Youngman, Jennifer Keys, Matthew J. Stoltz, Chun Chieh G. Chen, Daniel A. Chaves, Shenghua Duan, Kristin D. Kasschau, Noah Fahlgren, John R. Yates, Shohei Mitani, James C. Carrington, Craig C. Mello

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)231-244
Number of pages14
JournalMolecular cell
Issue number2
StatePublished - Oct 23 2009
Externally publishedYes


  • DNA
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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