Editors' ChoiceRNA INTERFERENCE

The Art of Transcriptional Gene Silencing

STKE  29 Aug 2006:
Vol. 2006, Issue 350, pp. tw299
DOI: 10.1126/stke.3502006tw299

RNA interference (RNAi) targets sequences to be silenced through complementary small interfering (si)RNAs. SiRNAs are bound by Ago proteins, some of which can "slice" and inactivate target RNAs. RNAi silences gene expression at both the posttranscriptional and transcriptional levels. In posttranscriptional gene silencing, siRNAs target mRNAs. The target of siRNAs in transcriptional gene silencing (TGS) could be either DNA or the RNA generated from it. Irvine et al. made mutations in the lone fission yeast Ago protein that prevent it from slicing. The mutant protein has a greatly diminished TGS activity, suggesting that siRNAs interact with nascent RNA rather than the DNA that encodes it to extinguish transcription. Furthermore, spreading of TGS to neighboring genes requires read-through transcription of the targeted and sliced nascent transcripts.

D. V. Irvine, M. Zaratiegui, N. H. Tolia, D. B. Goto, D. H. Chitwood, M. W. Vaughn, L. Joshua-Tor, R. A. Martienssen, Argonaute slicing is required for heterochromatic silencing and spreading. Science 313, 1134-1137 (2006). [Abstract] [Full Text]