Two classes of silencing RNAs move between Caenorhabditis elegans tissues

Nat Struct Mol Biol. 2011 Oct 9;18(11):1184-8. doi: 10.1038/nsmb.2134.

Abstract

Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism, but the identities of these mobile RNA species in animals are unknown. Here, we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in C. elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE-4, the endonuclease DCR-1, which cleaves long dsRNA into double-stranded short-interfering RNA (ds-siRNA), and the putative nucleotidyltransferase MUT-2 (RDE-3). However, single-stranded siRNA and downstream secondary siRNA produced upon amplification by the RNA-dependent RNA polymerase RRF-1 do not generate mobile silencing RNA. Restricting intertissue transport to long dsRNA and directly processed siRNA intermediates rather than amplified siRNA may serve to modulate the extent of systemic silencing in proportion to available dsRNA.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / anatomy & histology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Plants / genetics
  • RNA Interference
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • Recombinant Fusion Proteins