A slow RNA polymerase II affects alternative splicing in vivo
A slow RNA polymerase II affects alternative splicing in vivo
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DOI：
10.1016/j.molcel.2003.08.001
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发表时间：
2003-08-01
期刊：
影响因子：
16
通讯作者：
Kornblihtt, AR
中科院分区：
文献类型：
--
作者：
de la Mata, M;Alonso, CR;Kornblihtt, AR
启动子结构和占据的变化已被证明可以改变几个基因的剪接模式，证明转录和选择性剪接之间的耦合。已经提出启动子效应涉及RNA pol II延伸速率的调节。果蝇pol II最大亚基的C4点突变赋予酶较低的延伸率。在这里，我们表明，人类相当于果蝇的C4 pol II在人类培养细胞的表达影响选择性剪接的纤连蛋白EDI外显子和腺病毒E1a前mRNA。最重要的是，Hox基因Ultrabithorax的再剪接在果蝇胚胎C4突变体中受到刺激，这表明内源基因上的选择性剪接的转录控制。这些结果为选择性剪接在体内的延伸控制提供了直接的证据。
Changes in promoter structure and occupation have been shown to modify the splicing pattern of several genes, evidencing a coupling between transcription and alternative splicing. It has been proposed that the promoter effect involves modulation of RNA pol II elongation rates. The C4 point mutation of the Drosophila pol II largest subunit confers on the enzyme a lower elongation rate. Here we show that expression of a human equivalent to Drosophila's C4 pol II in human cultured cells affects alternative splicing of the fibronectin EDI exon and adenovirus E1a pre-mRNA. Most importantly, resplicing of the Hox gene Ultrabithorax is stimulated in Drosophila embryos mutant for C4, which demonstrates the transcriptional control of alternative splicing on an endogenous gene. These results provide a direct proof for the elongation control of alternative splicing in vivo.