Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome
Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome
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DOI：
10.1038/nsmb.1375
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发表时间：
2008-02-01
影响因子：
16.8
通讯作者：
Black, Douglas L.
中科院分区：
文献类型：
--
作者：
Sharma, Shalini;Kohlstaedt, Lori A.;Black, Douglas L.
聚嘧啶束结合蛋白（PTB）结合前mrna改变剪接位点的选择。我们研究了一系列剪接体复合物，它们在ptb介导的剪接抑制或不存在的条件下组装在pre-mRNA上。在缺乏抑制的情况下，外显子定义复合物在调控外显子下游组装，可以进展为剪接前A复合物和功能性剪接体。在ptb介导的抑制下，组装被阻止在a样复合体上，无法过渡到剪接体复合体。反式剪接实验表明，即使U1和U2小核核糖核蛋白颗粒（snRNPs）与上游和下游外显子正确结合，PTB的存在也会阻止两个外显子复合物的相互作用。这些复合物的蛋白质组学分析为外显子定义复合物提供了新的描述，并表明剪接调节因子可以作用于外显子定义复合物和内含子定义剪接体之间的过渡。
The polypyrimidine tract binding protein (PTB) binds pre-mRNAs to alter splice-site choice. We characterized a series of spliceosomal complexes that assemble on a pre-mRNA under conditions of either PTB-mediated splicing repression or its absence. In the absence of repression, exon definition complexes that were assembled downstream of the regulated exon could progress to pre-spliceosomal A complexes and functional spliceosomes. Under PTB-mediated repression, assembly was arrested at an A-like complex that was unable to transition to spliceosomal complexes. Trans-splicing experiments indicated that, even when the U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) are properly bound to the upstream and downstream exons, the presence of PTB prevents the interaction of the two exon complexes. Proteomic analyses of these complexes provide a new description of exon definition complexes, and indicate that splicing regulators can act on the transition between the exon definition complex and an intron-defined spliceosome.