Tudor Staphylococcal Nuclease (Tudor-SN) Participates in Small Ribonucleoprotein (snRNP) Assembly via Interacting with Symmetrically Dimethylated Sm Proteins
Tudor Staphylococcal Nuclease (Tudor-SN) Participates in Small Ribonucleoprotein (snRNP) Assembly via Interacting with Symmetrically Dimethylated Sm Proteins
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Tudor 葡萄球菌核酸酶 (Tudor-SN) 通过与对称二甲基化 Sm 蛋白相互作用参与小核糖核蛋白 (snRNP) 组装
DOI：
10.1074/jbc.m111.311852
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发表时间：
2012-05-25
影响因子：
4.8
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Gao, Xingjie;Zhao, Xiujuan;Yang, Jie
人Tudor葡萄球菌核酸酶（Tudor-SN）由葡萄球菌核酸酶（SN）样结构域的四个串联重复序列组成，随后是由两侧为两个部分SN样序列的中央Tudor组成的Tudor和SN样结构域（TSN）。晶体结构的都铎结构域显示一个保守的芳香族笼，这是预测挂钩甲基。在这里，我们证明了Tudor-SN的TSN结构域结合对称二甲基精氨酸（sDMA）修饰的SmB/B'和SmD 1/D3剪接体的核心蛋白。我们证明，这种相互作用的能力是由甲基转移酶抑制剂5-脱氧-5-（甲硫基）腺苷减少。突变实验表明TSN结构域甲基结合笼中的保守氨基酸（Phe-715、Tyr-721、Tyr-738和Tyr-741）是Tudor-SN-SmB相互作用所必需的。此外，Tudor-SN的耗尽影响Sm蛋白与snRNAs的关联，并因此抑制由Sm核心复合物介导的富含尿苷的小核糖核蛋白在体内的组装。我们的研究结果揭示了Tudor-SN参与调节小核核糖核蛋白生物合成的分子基础，这为Tudor-SN的生物活性提供了新的见解。
Human Tudor staphylococcal nuclease (Tudor-SN) is composed of four tandem repeats of staphylococcal nuclease (SN)-like domains, followed by a tudor and SN-like domain (TSN) consisting of a central tudor flanked by two partial SN-like sequences. The crystal structure of the tudor domain displays a conserved aromatic cage, which is predicted to hook methyl groups. Here, we demonstrated that the TSN domain of Tudor-SN binds to symmetrically dimethylarginine (sDMA)-modified SmB/B' and SmD1/D3 core proteins of the spliceosome. We demonstrated that this interaction ability is reduced by the methyltransferase inhibitor 5-deoxy-5-(methylthio)adenosine. Mutagenesis experiments indicated that the conserved amino acids (Phe-715, Tyr-721, Tyr-738, and Tyr-741) in the methyl-binding cage of the TSN domain are required for Tudor-SN-SmB interaction. Furthermore, depletion of Tudor-SN affects the association of Sm protein with snRNAs and, as a result, inhibits the assembly of uridine-rich small ribonucleoprotein mediated by the Sm core complex in vivo. Our results reveal the molecular basis for the involvement of Tudor-SN in regulating small nuclear ribonucleoprotein biogenesis, which provides novel insight related to the biological activity of Tudor-SN.