Efficient RNA polymerase II pause release requires U2 snRNP function
Efficient RNA polymerase II pause release requires U2 snRNP function
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DOI：
10.1016/j.molcel.2021.02.016
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发表时间：
2021-05-06
期刊：
影响因子：
16
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Caizzi, Livia;Monteiro-Martins, Sara;Cramer, Patrick
RNA聚合酶II（Pol II）的转录与前体mRNA剪接相结合，但其潜在机制仍知之甚少。共转录剪接需要在新生前mRNA上组装功能性剪接体，但这是否以及如何影响Pol II转录仍不清楚。在这里，我们表明，抑制前mRNA分支位点识别的剪接体组件U2 snRNP导致广泛和强烈的减少，在新的RNA合成从人类基因。多组学分析表明，U2 snRNP功能的抑制增加了启动子近端区域的Pol II暂停的持续时间，损害了暂停释放因子- EFb的募集，并降低了Pol II在基因起始处的延伸速度。我们的研究结果表明，有效地释放暂停Pol II到活跃的转录延伸需要形成的功能spliceosomes和真核mRNA的生物合成依赖于正反馈的剪接机器的转录机器。
Transcription by RNA polymerase II (Pol II) is coupled to pre-mRNA splicing, but the underlying mechanisms remain poorly understood. Co-transcriptional splicing requires assembly of a functional spliceosome on nascent pre-mRNA, but whether and how this influences Pol II transcription remains unclear. Here we show that inhibition of pre-mRNA branch site recognition by the spliceosome component U2 snRNP leads to a widespread and strong decrease in new RNA synthesis from human genes. Multiomics analysis reveals that inhibition of U2 snRNP function increases the duration of Pol II pausing in the promoter-proximal region, impairs recruitment of the pause release factor - EFb, and reduces Pol II elongation velocity at the beginning of genes. Our results indicate that efficient release of paused Pol II into active transcription elongation requires the formation of functional spliceosomes and that eukaryotic mRNA biogenesis relies on positive feedback from the splicing machinery to the transcription machinery.