The Chp1-Tas3 core is a multifunctional platform critical for gene silencing by RITS

Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 11/2011; 18(12):1351-7. DOI: 10.1038/nsmb.2151
Source: PubMed


RNA interference (RNAi) is critical for the assembly of heterochromatin at Schizosaccharomyces pombe centromeres. Central to this process is the RNA-induced initiation of transcriptional gene silencing (RITS) complex, which physically anchors small noncoding RNAs to chromatin. RITS includes Ago1, the chromodomain protein Chp1, and Tas3, which forms a bridge between Chp1 and Ago1. Chp1 is a large protein with no recognizable domains, apart from its chromodomain. Here we describe how the structured C-terminal half of Chp1 binds the Tas3 N-terminal domain, revealing the tight association of Chp1 and Tas3. The structure also shows a PIN domain at the C-terminal tip of Chp1 that controls subtelomeric transcripts through a post-transcriptional mechanism. We suggest that the Chp1-Tas3 complex provides a solid and versatile platform to recruit both RNAi-dependent and RNAi-independent gene-silencing pathways for locus-specific regulation of heterochromatin.

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Available from: Thomas Schalch, Dec 15, 2013
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    • "Consistent with this, the level of siRNAs is reduced in mutants of the ClrC complex, presumably due to dissociation of the RITS from H3K9me-deficient heterochromatin in these mutants (Motamedi et al., 2004; Hong et al., 2005; Li et al., 2005). Tas3 serves as a backbone for the RITS complex, linking Chp1 and Ago1 (Schalch et al., 2011). The C-terminal end of Tas3 contains an α-helical motif which can assemble into a helical polymer that is essential for the cis spreading of the RITS complex at peri-centromeres (Li et al., 2009). "
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