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

Mikael Feracci, Jaelle N. Foot, Sushma N. Grellscheid, Marina Danilenko, Ralf Stehle, Oksana Gonchar, Hyun Seo Kang, Caroline Dalgliesh, N. Helge Meyer, Yilei Liu, Albert Lahat, Michael Sattler, Ian C. Eperon, David J. Elliott, Cyril Dominguez

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish
Article number10355
JournalNature Communications
Volume7
DOIs
StatePublished - 13 Jan 2016

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