title: The Chp1-Tas3 core is a multifunctional platform critical for gene silencing by RITS.
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.
authors.affiliation: Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schalch
authors.forename: Godwin
authors.initials: G
authors.lastname: Job
authors.forename: Sreenath
authors.initials: S
authors.lastname: Shanker
authors.forename: Janet F
authors.initials: JF
authors.lastname: Partridge
authors.forename: Leemor
authors.initials: L
authors.lastname: Joshua-Tor
mesh_terms: D000595:Amino Acid Sequence; D060565:Argonaute Proteins / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology*; D008958:Models, Molecular; D005810:Multigene Family; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference / Q000502:physiology; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: C481643:Ago1 protein, S pombe; D060565:Argonaute Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C115018:Chp1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C499720:Tas3 protein, S pombe
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