The SRm160/300 splicing coactivator is required for exon-enhancer function
The SRm160/300 splicing coactivator is required for exon-enhancer function
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DOI：
10.1073/pnas.96.11.6125
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发表时间：
1999-05-25
影响因子：
11.1
通讯作者：
Blencowe, BJ
中科院分区：
文献类型：
--
作者：
Eldridge, AG;Li, Y;Blencowe, BJ
外显子剪接增强子（ESE）序列是识别前mrna剪接位点的重要手段。这些序列由特定的丝氨酸-精氨酸（SR）重复蛋白结合，促进剪接复合物在邻近剪接位点的组装。我们最近发现了一个剪接“共激活子”SRm160/300，它包含SRm160 （160 kDa的SR核基质蛋白）和300 kDa的核基质抗原。在本研究中，我们发现SRm160/300是富含嘌呤的ESE促进来自果蝇双性基因的pre-mRNA剪接所必需的。SRm160/300和U2小核核糖核蛋白颗粒（snRNP）与该前mrna的结合需要U1 snRNP和与ESE结合的因子。独立于pre-mRNA， SRm160/300特异性地与U2 snRNP和果蝇选择性剪接调节剂Transformer 2的人类同源物相互作用，后者与富含嘌呤的ESEs结合。结果表明，在ESE功能模型中，SRm160/300剪接共激活子促进ESE结合的“激活子”与剪接体的snRNP机制之间的关键相互作用。
Exonic splicing enhancer (ESE) sequences are important for the recognition of splice sites in pre-mRNA. These sequences are bound by specific serine-arginine (SR) repeat proteins that promote the assembly of splicing complexes at adjacent splice sites. We have recently identified a splicing "coactivator," SRm160/300, which contains SRm160 (the SR nuclear matrix protein of 160 kDa) and a 300-kDa nuclear matrix antigen. In the present study, we show that SRm160/300 is required for a purine-rich ESE to promote the splicing of a pre-mRNA derived from the Drosophila doublesex gene. The association of SRm160/300 and U2 small nuclear ribonucleoprotein particle (snRNP) with this pre-mRNA requires both U1 snRNP and factors bound to the ESE. Independently of pre-mRNA, SRm160/300 specifically interacts with U2 snRNP and with a human homolog of the Drosophila alternative splicing regulator Transformer 2, which binds to purine-rich ESEs. The results suggest a model for ESE function in which the SRm160/300 splicing coactivator promotes critical interactions between ESE-bound "activators" and the snRNP machinery of the spliceosome.