RBM5/Luca-15/H37 Regulates Fas Alternative Splice Site Pairing after Exon Definition
RBM5/Luca-15/H37 Regulates Fas Alternative Splice Site Pairing after Exon Definition
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DOI：
10.1016/j.molcel.2008.08.008
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发表时间：
2008-10-10
期刊：
影响因子：
16
通讯作者：
Valcarcel, Juan
中科院分区：
文献类型：
--
作者：
Bonnal, Sophie;Martinez, Concepcion;Valcarcel, Juan
RBM5/Luca-15/H37 是一种在肺癌中经常失活并在乳腺肿瘤中过度表达的基因。其蛋白质产物已在前剪接体复合物中检测到，并调节细胞增殖和 Fas 介导的细胞凋亡。我们报告说，RBM5 是参与 3' 剪接位点识别的复合物的一个组成部分，并调节凋亡相关基因（包括 Fas 受体）的选择性剪接，在程序性细胞死亡中具有拮抗功能的异构体之间进行切换。与剪接调节的经典机制相反，RBM5 不会影响导致 Fas 外显子 6 定义的剪接位点识别的早期事件。相反，RBM5 抑制围绕外显子 6 组装的前剪接体复合物到在侧翼内含子上组装的成熟剪接体之间的转变，并促进远端剪接位点的序列特异性配对。对于 RBM5 功能很重要的 OCRE 结构域接触 U4/5/6 tri-snRNP 的组件，这与 RBM5 在前剪接体组装和外显子定义后调节剪接位点配对的想法一致。一个到
RBM5/Luca-15/H37 is a gene frequently inactivated in lung cancers and overexpressed in breast tumors. Its protein product has been detected in prespliceosomal complexes and modulates cell proliferation and Fas-mediated apoptosis. We report that RBM5 is a component of complexes involved in 3' splice site recognition and regulates alternative splicing of apoptosis-related genes, including the Fas receptor, switching between isoforms with antagonistic functions in programmed cell death. In contrast with classical mechanisms of splicing regulation, RBM5 does not affect early events of splice site recognition that lead to Fas exon 6 definition. Instead, RBM5 inhibits the transition between prespliceosomal complexes assembled around exon 6 to mature spliceosomes assembled on the flanking introns and promotes sequence-specific pairing of the distal splice sites. An OCRE domain important for RBM5 function contacts components of the U4/5/6 tri-snRNP, consistent with the idea that RBM5 modulates splice site pairing after prespliceosome assembly and exon definition. a to