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Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing.

Abstract : In the fission yeast Schizosaccharomyces pombe, the RNA-Induced Transcriptional Silencing (RITS) complex has been proposed to target the chromosome via siRNA-dependent base-pairing interactions to initiate heterochromatin formation. Here we show that tethering of the RITS subunit, Tas3, to the RNA transcript of the normally active ura4+ gene silences ura4+ expression. This silencing depends on a functional RNAi pathway, requires the heterochromatin proteins, Swi6/HP1, Clr4/Suv39h, and Sir2, and is accompanied by the generation of ura4+ siRNAs, histone H3-lysine 9 methylation, and Swi6 binding. Furthermore, the ability of the newly generated ura4+ siRNAs to silence a second ura4+ allele in trans is strongly inhibited by the conserved siRNA nuclease, Eri1. Surprisingly, silencing of tethered ura4+, or ura4+ inserted within centromeric heterochromatin, or some of the endogenous centromeric repeat promoters, is not associated with changes in RNA polymerase II occupancy. These findings support a model in which targeting of nascent transcripts by RITS mediates chromatin modifications and suggest that cotranscriptional processing events play a primary role in the silencing mechanism.
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Contributor : Andre Verdel Connect in order to contact the contributor
Submitted on : Monday, October 20, 2008 - 4:48:43 PM
Last modification on : Tuesday, October 21, 2008 - 11:13:22 AM

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Marc Bühler, André Verdel, Danesh Moazed. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing.. Cell, Elsevier, 2006, 125 (5), pp.873-86. ⟨10.1016/j.cell.2006.04.025⟩. ⟨inserm-00332367⟩



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