SR proteins function in coupling RNAP II transcription to pre-mRNA splicing
SR proteins function in coupling RNAP II transcription to pre-mRNA splicing
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DOI：
10.1016/j.molcel.2007.05.036
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发表时间：
2007-06-22
期刊：
影响因子：
16
通讯作者：
Reed, Robin
中科院分区：
文献类型：
--
作者：
Das, Rita;Yu, Jiong;Reed, Robin
转录和剪接在功能上偶联，导致RNA聚合酶II （RNAP II）转录物的高效剪接。这种耦合所涉及的机制尚不清楚。为了确定潜在的偶联因子，我们对免疫纯化的人RNAP II进行了全面的蛋白质组学分析，鉴定出bbb100特异性相关蛋白。其中包括SR蛋白剪接因子家族和U1 snRNP的所有组分，但没有其他snRNPs或剪接因子。我们发现SR蛋白在转录与剪接的耦合中起作用，并提供证据表明其机制涉及SR蛋白对RNAP II转录物的共转录募集。我们提出，U1 snRNP/SR蛋白与RNAP II的独家关联将这些剪接因子定位在接近新生的pre-mRNA的位置，这些剪接因子已知在剪接体组装的早期起作用。因此，这些因子很容易战胜抑制hnRNP蛋白，导致在新生RNAP II转录本上有效的剪接体组装。
Transcription and splicing are functionally coupled, resulting in highly efficient splicing of RNA polymerase II (RNAP II) transcripts. The mechanism involved in this coupling is not known. To identify potential coupling factors, we carried out a comprehensive proteomic analysis of immunopurified human RNAP II, identifying > 100 specifically associated proteins. Among these are the SR protein family of splicing factors and all of the components of U1 snRNP, but no other snRNPs or splicing factors. We show that SR proteins function in coupling transcription to splicing and provide evidence that the mechanism involves cotranscriptional recruitment of SR proteins to RNAP II transcripts. We propose that the exclusive association of U1 snRNP/SR proteins with RNAP II positions these splicing factors, which are known to function early in spliceosome assembly, close to the nascent pre-mRNA. Thus, these factors readily out-compete inhibitory hnRNP proteins, resulting in efficient spliceosome assembly on nascent RNAP II transcripts.