Bonnal Sophie, Martínez Concepción, Förch Patrik, Bachi Angela, Wilm Matthias, Valcárcel Juan
Centre de Regulació Genòmica, Dr. Aigüader, 88 08003 Barcelona, Spain.
Mol Cell. 2008 Oct 10;32(1):81-95. doi: 10.1016/j.molcel.2008.08.008.
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.
RBM5/Luca-15/H37是一种在肺癌中经常失活而在乳腺肿瘤中过表达的基因。其蛋白质产物已在剪接体前体复合物中被检测到，并可调节细胞增殖和Fas介导的细胞凋亡。我们报告称，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的可变剪接，包括Fas受体，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。与经典的剪接调控机制不同，RBM5不影响导致Fas外显子6定义的剪接位点识别早期事件。相反，RBM5抑制围绕外显子6组装的剪接体前体复合物向侧翼内含子上组装的成熟剪接体的转变，并促进远端剪接位点的序列特异性配对。对RBM5功能重要的OCRE结构域与U4/5/6三小核核糖核蛋白的成分接触，这与RBM5在剪接体前体组装和外显子定义后调节剪接位点配对的观点一致。
