The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans

Genes Dev. 2012 Apr 15;26(8):846-56. doi: 10.1101/gad.180679.111.

Abstract

The molecular mechanisms for target mRNA degradation in Caenorhabditis elegans undergoing RNAi are not fully understood. Using a combination of genetic, proteomic, and biochemical approaches, we report a divergent RDE-10/RDE-11 complex that is required for RNAi in C. elegans. Genetic analysis indicates that the RDE-10/RDE-11 complex acts in parallel to nuclear RNAi. Association of the complex with target mRNA is dependent on RDE-1 but not RRF-1, suggesting that target mRNA recognition depends on primary but not secondary siRNA. Furthermore, RDE-11 is required for mRNA degradation subsequent to target engagement. Deep sequencing reveals a fivefold decrease in secondary siRNA abundance in rde-10 and rde-11 mutant animals, while primary siRNA and microRNA biogenesis is normal. Therefore, the RDE-10/RDE-11 complex is critical for amplifying the exogenous RNAi response. Our work uncovers an essential output of the RNAi pathway in C. elegans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference*
  • RNA Stability / genetics*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / biosynthesis
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Nuclear Proteins
  • RDE-10 protein, C elegans
  • RDE-11 protein, C elegans
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins