Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome
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DOI：
10.1016/j.molcel.2019.04.034
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发表时间：
2018-05
期刊：
影响因子：
16
通讯作者：
Nicolas Viphakone;I. Sudbery;Catherine G. Heath;D. Sims;Stuart A. Wilson
中科院分区：
文献类型：
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作者：
Nicolas Viphakone;I. Sudbery;Catherine G. Heath;D. Sims;Stuart A. Wilson
在基因表达过程中，RNA输出因子主要是驱动核胞质转运。虽然早期的研究表明外显子连接复合体（EJC）为它们提供了一个结合平台，但随后的工作表明，它们仅被帽结合复合体招募到rna的5 '端，作为TREX的一部分。使用iCLIP，我们发现输出受体Nxf1和两个TREX亚基Alyref和Chtop通过剪接被募集到整个mRNA共转录，但在3 '端加工之前。因此，Alyref改变剪接决定，Chtop调节选择性聚腺苷化。Alyref被CBC招募到rna的5 '端，我们的数据显示随后与EJCs附近的rna结合。我们证明eIF4A3不仅在靠近EJC位点的剪接rna上刺激Alyref沉积，而且在单外显子转录本上也刺激Alyref沉积。我们的研究揭示了mRNA输出因子的共转录募集的机制见解，以及这如何塑造人类转录组。
During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform for them, subsequent work proposed that they are only recruited by the cap binding complex to the 5′ end of RNAs, as part of TREX. Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are recruited to the whole mRNA co-transcriptionally via splicing but before 3′ end processing. Consequently, Alyref alters splicing decisions and Chtop regulates alternative polyadenylation. Alyref is recruited to the 5′ end of RNAs by CBC, and our data reveal subsequent binding to RNAs near EJCs. We demonstrate that eIF4A3 stimulates Alyref deposition not only on spliced RNAs close to EJC sites but also on single-exon transcripts. Our study reveals mechanistic insights into the co-transcriptional recruitment of mRNA export factors and how this shapes the human transcriptome.