Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline

Mol Cell. 2009 Oct 23;36(2):231-44. doi: 10.1016/j.molcel.2009.09.020. Epub 2009 Oct 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Genome / genetics*
  • Germ Cells / metabolism*
  • Models, Genetic
  • Molecular Sequence Data
  • Phylogeny
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA Replicase / metabolism
  • RNA, Helminth / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism*
  • Sequence Analysis, RNA
  • Temperature

Substances

  • Caenorhabditis elegans Proteins
  • RNA, Helminth
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA Replicase