Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi

Curr Biol. 2002 Aug 6;12(15):1317-9. doi: 10.1016/s0960-9822(02)01041-2.


RNA interference (RNAi) is a broadly used reverse genetics method in C. elegans. Unfortunately, RNAi does not inhibit all genes. We show that loss of function of a putative RNA-directed RNA polymerase (RdRP) of C. elegans, RRF-3, results in a substantial enhancement of sensitivity to RNAi in diverse tissues. This is particularly striking in the nervous system; neurons that are generally refractory to RNAi in a wild-type genetic background can respond effectively to interference in an rrf-3 mutant background. These data provide the first indication of physiological negative modulation of the RNAi response and implicate an RdRP-related factor in this effect. The rrf-3 strain can be useful to study genes that, in wild-type, do not show a phenotype after RNAi, and it is probably the strain of choice for genome-wide RNAi screens.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics*
  • Phenotype
  • RNA Interference*
  • RNA, Double-Stranded / genetics
  • RNA-Dependent RNA Polymerase / deficiency
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism*


  • RNA, Double-Stranded
  • RNA-Dependent RNA Polymerase
  • RNA-directed RNA polymerase RRF-3, C elegans