title: Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68.
abstract: Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins. T-STAR is a tissue-specific paralogue that regulates the alternative splicing of neuronal pre-mRNAs. STAR proteins differ from most splicing factors, in that they contain a single RNA-binding domain. Their specificity of RNA recognition is thought to arise from their property to homodimerize, but how dimerization influences their function remains unknown. Here, we establish at atomic resolution how T-STAR and Sam68 bind to RNA, revealing an unexpected mode of dimerization different from other members of the STAR family. We further demonstrate that this unique dimerization interface is crucial for their biological activity in splicing regulation, and suggest that the increased RNA affinity through dimer formation is a crucial parameter enabling these proteins to select their functional targets within the transcriptome.
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Mikael
authors.initials: M
authors.lastname: Feracci
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Jaelle N
authors.initials: JN
authors.lastname: Foot
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
authors.forename: Sushma N
authors.initials: SN
authors.lastname: Grellscheid
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Danilenko
authors.affiliation: Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Lichtenbergstr. 4, DE-85747 Garching, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Stehle
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Oksana
authors.initials: O
authors.lastname: Gonchar
authors.affiliation: Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Lichtenbergstr. 4, DE-85747 Garching, Germany.|Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, DE-85764 Oberschleißheim, Germany.
authors.forename: Hyun-Seo
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dalgliesh
authors.affiliation: Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Lichtenbergstr. 4, DE-85747 Garching, Germany.|Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, DE-85764 Oberschleißheim, Germany.
authors.forename: N Helge
authors.initials: NH
authors.lastname: Meyer
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Lahat
authors.affiliation: Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Lichtenbergstr. 4, DE-85747 Garching, Germany.|Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, DE-85764 Oberschleißheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Eperon
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elliott
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Cyril
authors.initials: C
authors.lastname: Dominguez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; C118777:KHDRBS3 protein, human; D016601:RNA-Binding Proteins; D012313:RNA