Interference in the Secondary

Science's STKE  16 Jan 2007:
Vol. 2007, Issue 369, pp. tw25
DOI: 10.1126/stke.3692007tw25

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.

J. Pak, A. Fire, Distinct populations of primary and secondary effectors during RNAi in C. elegans. Science 315, 241-244 (2007). [Abstract] [Full Text]

T. Sijen, F. A. Steiner, K. L. Thijssen, R. H. A. Plasterk, Secondary siRNAs result from unprimed RNA synthesis and form a distinct class. Science 315, 244-247 (2007). [Abstract] [Full Text]

D. C. Baulcombe, Amplified silencing. Science 315, 199-200 (2007). [Summary] [Full Text]