The effector molecules in RNA interference (RNAi) are small interfering RNAs (siRNAs). The initial population of "primary" siRNAs, ~22 nucleotides in length with 5′-monophosphates groups, is generated by the Dicer nuclease. Amplification and "spreading" of the initial trigger population are thought to contribute to strength of the RNAi response in a number of systems and involve an RNA-dependent RNA polymerase (RDRP) (see the Perspective by Baulcombe). To investigate the nature of this secondary response, Pak and Fire and Sijen et al. analyzed the course of an experimentally induced RNAi reaction in the nematode worm Caenorhabditis elegans and also examined endogenous small RNAs. They found distinct populations of "secondary" siRNAs that are antisense to the messenger RNA target, that have a di- or triphosphate moiety at their 5′ ends, and that may map both upstream and downstream of the original dsRNA trigger. Primary siRNAs do not appear to act as primers for RdRP but rather guide RdRP to targeted messages for the de novo synthesis of secondary siRNAs that further boost the RNAi response.
- Interference in the Secondary
In RNA-directed gene silencing in worms, an unanticipated class of small antisense RNAs is synthesized by cellular RNA-directed RNA polymerase.Permalink: