Promoter-proximal pausing mediated by the exon junction complex regulates splicing.,Nature Communications

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Promoter-proximal pausing mediated by the exon junction complex regulates splicing.
Nature Communications ( IF 14.7 ) Pub Date : 2019-01-31 , DOI: 10.1038/s41467-019-08381-0
Junaid Akhtar _{1,

2} , Nastasja Kreim ₃ , Federico Marini ₄ , Giriram Mohana ₁ , Daniel Brüne ₁ , Harald Binder ₅ , Jean-Yves Roignant ₁

Affiliation

Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition.

中文翻译：

外显子连接复合物介导的启动子近端暂停调节剪接。

RNA聚合酶II（Pol II）的启动子近端暂停是跨后生动物的广泛转录调控步骤。在这里，我们发现核外显子连接复合体（EJC前）是该过程的关键且保守的调节剂。EJC前亚基的耗竭导致Pol II暂停的总体减少，并导致过早进入延长期。该作用至少部分地通过在启动子处非典型的EJC前成分的募集而发生。未能在启动子处募集前EJC会导致正转录延伸复合物（P-TEFb）的结合增加，并导致Pol II释放增强。值得注意的是，恢复暂停足以挽救外显子跳跃和与体内EJC前成分耗尽相关的光感受器分化缺陷。

更新日期：2019-01-31

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