On the role of RNA amplification in dsRNA-triggered gene silencing

Cell. 2001 Nov 16;107(4):465-76. doi: 10.1016/s0092-8674(01)00576-1.


We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5'-->3' on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bacterial Proteins*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Endoribonucleases / physiology
  • Gene Silencing / physiology*
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Models, Genetic*
  • RNA, Double-Stranded / physiology*
  • RNA, Helminth / physiology*
  • RNA, Small Interfering
  • RNA, Untranslated / physiology*
  • RNA-Directed DNA Polymerase / physiology*
  • Recombinant Fusion Proteins / physiology
  • Ribonuclease III
  • Sequence Deletion
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transgenes


  • Bacterial Proteins
  • Helminth Proteins
  • RNA, Double-Stranded
  • RNA, Helminth
  • RNA, Small Interfering
  • RNA, Untranslated
  • Recombinant Fusion Proteins
  • Transcription Factors
  • frr1 protein, Lactococcus lactis
  • RNA-Directed DNA Polymerase
  • Endoribonucleases
  • Ribonuclease III