Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68.
Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68.
复制标题
DOI：
10.1038/ncomms10355
复制
发表时间：
2016-01-13
影响因子：
16.6
通讯作者：
Dominguez C
中科院分区：
文献类型：
--
作者：
Feracci M;Foot JN;Grellscheid SN;Danilenko M;Stehle R;Gonchar O;Kang HS;Dalgliesh C;Meyer NH;Liu Y;Lahat A;Sattler M;Eperon IC;Elliott DJ;Dominguez C
Sam 68和T-星星是星星蛋白家族的成员，其直接将信号转导与转录后基因调控联系起来。Sam 68控制许多致癌蛋白的选择性剪接。T-STAR是一种调节神经元前体mRNA选择性剪接的组织特异性蛋白。星星蛋白与大多数剪接因子的不同之处在于它们含有单个RNA结合结构域。它们识别RNA的特异性被认为是由它们的同源二聚化特性引起的，但二聚化如何影响它们的功能仍然未知。在这里，我们建立在原子分辨率的T-星星和Sam 68如何绑定到RNA，揭示了一个意想不到的模式，不同于其他成员的星星家庭的二聚化。我们进一步证明，这种独特的二聚化界面是至关重要的剪接调控的生物活性，并建议通过二聚体形成增加RNA亲和力是一个关键参数，使这些蛋白质选择其功能的目标内的转录。 Sam 68和T-星星是星星蛋白家族的成员，其调节RNA代谢的各个方面。在这里，作者揭示了这些蛋白质的选择性剪接调控所需的结构特征。
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.