CGC Bibliography Paper 4981

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

Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S, Timmons L, Plasterk RHA, Fire A

Medline:

11719187

Citation:

Cell 107: 465-476 2001

Type:

ARTICLE

Genes:

ego-1 mut-7 par-1 pop-1 pos-1 rde-1 rde-4 rrf-1 rrf-2 rrf-3 unc-15 unc-22 unc-52

Abstract:

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.