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Nat Commun. 2016 Jan 13;7:10355. doi: 10.1038/ncomms10355.

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

Author information

1
Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK.
2
Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle NE1 3BZ, UK.
3
Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Lichtenbergstr. 4, DE-85747 Garching, Germany.
4
Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, DE-85764 Oberschleißheim, Germany.
5
School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, UK.

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.

PMID:
26758068
PMCID:
PMC4735526
DOI:
10.1038/ncomms10355
[Indexed for MEDLINE]
Free PMC Article

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