title: Sequence-specific recognition of RNA hairpins by the SAM domain of Vts1p.
abstract: The SAM domain of the Saccharomyces cerevisiae post-transcriptional regulator Vts1p epitomizes a subfamily of SAM domains conserved from yeast to humans that function as sequence-specific RNA-binding domains. Here we report the 2.0-A X-ray structure of the Vts1p SAM domain bound to a high-affinity RNA ligand. Specificity of RNA binding arises from the association of a guanosine loop base with a shallow pocket on the SAM domain and from multiple SAM domain contacts to the unique backbone structure of the loop, defined in part by a nonplanar base pair within the loop. We have validated NNF1 as an endogenous target of Vts1p among 79 transcripts that copurify with Vts1p. Bioinformatic analysis of these mRNAs demonstrates that the RNA-binding specificity of Vts1p in vivo is probably more stringent than that of the isolated SAM domain in vitro.
authors.affiliation: Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, M5G 1X5, Canada.
authors.forename: Tzvi
authors.initials: T
authors.lastname: Aviv
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.forename: Giora
authors.initials: G
authors.lastname: Ben-Ari
authors.forename: Craig A
authors.initials: CA
authors.lastname: Smibert
authors.forename: Frank
authors.initials: F
authors.lastname: Sicheri
mesh_terms: D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D020407:Internet; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C508663:Vts1 protein, S cerevisiae