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Distinct populations of primary and secondary effectors during RNAi in C. elegans

Science. 2007 Jan 12;315(5809):241-4. doi: 10.1126/science.1132839. Epub 2006 Nov 23.

Abstract

RNA interference (RNAi) is a phylogenetically widespread gene-silencing process triggered by double-stranded RNA. In plants and Caenorhabditis elegans, two distinct populations of small RNAs have been proposed to participate in RNAi: "Primary siRNAs" (derived from DICER nuclease-mediated cleavage of the original trigger) and "secondary siRNAs" [additional small RNAs whose synthesis requires an RNA-directed RNA polymerase (RdRP)]. Analyzing small RNAs associated with ongoing RNAi in C. elegans, we found that secondary siRNAs constitute the vast majority. The bulk of secondary siRNAs exhibited structure and sequence indicative of a biosynthetic mode whereby each molecule derives from an independent de novo initiation by RdRP. Analysis of endogenous small RNAs indicated that a fraction derive from a biosynthetic mechanism that is similar to that of secondary siRNAs formed during RNAi, suggesting that small antisense transcripts derived from cellular messenger RNAs by RdRP activity may have key roles in cellular regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Cloning, Molecular
  • MicroRNAs / metabolism
  • Models, Genetic
  • RNA Interference*
  • RNA, Antisense / biosynthesis
  • RNA, Antisense / chemistry
  • RNA, Antisense / metabolism
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Helminth / chemistry
  • RNA, Helminth / genetics
  • RNA, Helminth / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / biosynthesis
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / metabolism*
  • RNA-Dependent RNA Polymerase / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • RNA, Antisense
  • RNA, Double-Stranded
  • RNA, Helminth
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Dependent RNA Polymerase