U2AF-homology motif interactions are required for alternative splicing regulation by SPF45
U2AF-homology motif interactions are required for alternative splicing regulation by SPF45
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DOI：
10.1038/nsmb1260
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发表时间：
2007-07-01
影响因子：
16.8
通讯作者：
Sattler, Michael
中科院分区：
文献类型：
--
作者：
Corsini, Lorenzo;Bonnal, Sophie;Sattler, Michael
yU 2AF-同源基序（UHM）介导参与组成性RNA剪接的因子之间的蛋白质-蛋白质相互作用。在这里，我们报告，剪接因子SPF 45调节选择性剪接的凋亡调控基因FAS（也称为CD 95）。SPF 45 UHM是该活性所必需的，并且结合存在于3'剪接位点识别因子U2 AF 65、SF 1和SF 3bl 55中的UHM-配体基序（ULM）。我们描述了一个2.1埃的晶体结构的SPF 45- UHM的复合物与乌尔姆肽从SF 3b 155。与先前描述的UHM-乌尔姆结构的特征不同的特征允许在SPF 45 UHM中设计突变，其选择性地损害与单个ULM的结合。使用乌尔姆选择性SPF 45变体的剪接测定证明，个体UHM-乌尔姆相互作用是SPF 45在体内进行FAS剪接调节所必需的。我们的数据表明，UHM-乌尔姆相互作用的网络参与调节可变剪接。
yThe U2AF- homology motif ( UHM) mediates protein- protein interactions between factors involved in constitutive RNA splicing. Here we report that the splicing factor SPF45 regulates alternative splicing of the apoptosis regulatory gene FAS ( also called CD95). The SPF45 UHM is necessary for this activity and binds UHM- ligand motifs ( ULMs) present in the 3' splice site recognizing factors U2AF65, SF1 and SF3b155. We describe a 2.1- angstrom crystal structure of SPF45- UHM in complex with a ULM peptide from SF3b155. Features distinct from those of previously described UHM- ULM structures allowed the design of mutations in the SPF45 UHM that selectively impair binding to individual ULMs. Splicing assays using the ULM- selective SPF45 variants demonstrate that individual UHM- ULM interactions are required for FAS splicing regulation by SPF45 in vivo. Our data suggest that networks of UHM- ULM interactions are involved in regulating alternative splicing.