RNA polymerase IIC-terminal domain mediates regulation of alternative splicing by SRp20
RNA polymerase IIC-terminal domain mediates regulation of alternative splicing by SRp20
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DOI：
10.1038/nsmb1155
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发表时间：
2006-11-01
影响因子：
16.8
通讯作者：
Kornblihtt, Alberto R.
中科院分区：
文献类型：
--
作者：
de la Mata, Manuel;Kornblihtt, Alberto R.
以前的研究已经将RNA聚合酶II的C末端结构域(CTD)与共转录前体信使RNA的加工联系在一起，但对CTD在调节选择性剪接中的功能知之甚少。我们已经使用耐α-Amanitin的polII CTD突变体和纤维连接蛋白报告迷你基因来研究这一功能。我们发现，CTD是丝氨酸/富含精氨酸(SR)蛋白SRp20抑制成熟mRNA中纤维连接蛋白盒外显子的作用所必需的。CTD磷酸化控制转录延长，这是选择性剪接调控的主要因素。然而，当转录伸长降低时，仍然可以观察到SRp20的作用。这些结果表明，CTD通过招募SRp20促进外显子跳跃，并且这独立于延伸对选择性剪接的转录控制起作用。
Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II (pol II) with cotranscriptional precursor messenger RNA processing, but little is known about the CTD's function in regulating alternative splicing. We have examined this function using alpha-amanitin-resistant pol II CTD mutants and fibronectin reporter minigenes. We found that the CTD is required for the inhibitory action of the serine/arginine-rich (SR) protein SRp20 on the inclusion of a fibronectin cassette exon in the mature mRNA. CTD phosphorylation controls transcription elongation, which is a major contributor to alternative splicing regulation. However, the effect of SRp20 is still observed when transcription elongation is reduced. These results suggest that the CTD promotes exon skipping by recruiting SRp20 and that this contributes independently of elongation to the transcriptional control of alternative splicing.