Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68

• Published in: Nature communications Vol. 7; no. 1; p. 10355
• Main Authors: Feracci, Mikael, Foot, Jaelle N., Grellscheid, Sushma N., Danilenko, Marina, Stehle, Ralf, Gonchar, Oksana, Kang, Hyun-Seo, Dalgliesh, Caroline, Meyer, N. Helge, Liu, Yilei, Lahat, Albert, Sattler, Michael, Eperon, Ian C., Elliott, David J., Dominguez, Cyril
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-01-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 38/77; 631/337/1645/1792; 631/45/535; 82/6; 82/80; Adaptor Proteins, Signal Transducing - metabolism; Alternative Splicing; Amino Acid Sequence; Animals; Biology; Cyclin-dependent kinases; Dimerization; DNA-Binding Proteins - metabolism; HEK293 Cells; Humanities and Social Sciences; Humans; Kinases; Male; Metabolism; Mice; Molecular Sequence Data; multidisciplinary; Nucleotide Motifs; Protein Structure, Tertiary; Proteins; RNA - metabolism; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Signal transduction; Spectrum analysis; Structure-Activity Relationship; United Kingdom > UK; Germany
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10355

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.
Sam68 and T-STAR are members of the STAR family of proteins, which regulate various aspects of RNA metabolism. Here, the authors reveal structural features required for alternative splicing regulation by these proteins.