The Chp1-Tas3 Core Is a Multifunctional Platform Critical for Gene Silencing by RITS

Nat Struct Mol Biol. 2011 Nov 13;18(12):1351-7. doi: 10.1038/nsmb.2151.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Argonaute Proteins / metabolism
  • Argonaute Proteins / physiology
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Gene Silencing / physiology*
  • Models, Molecular
  • Multigene Family
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • RNA Interference / physiology
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism
  • Schizosaccharomyces pombe Proteins / physiology*
  • Sequence Alignment
  • Sequence Analysis, Protein

Substances

  • Ago1 protein, S pombe
  • Argonaute Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chp1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Tas3 protein, S pombe

Associated data

  • PDB/3TIX