The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export
The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export
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mRNA 输出受体 NXF1 协调转录动力学、选择性多聚腺苷酸化和 mRNA 输出
DOI：
10.1016/j.molcel.2019.01.026
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发表时间：
2019-04-04
期刊：
影响因子：
16
通讯作者：
Cheng, Hong
中科院分区：
文献类型：
--
作者：
Chen, Suli;Wang, Ruijia;Cheng, Hong
选择性聚腺苷化（APA）产生具有不同3' UTR长度的mRNA亚型。先前的研究表明，3'端加工和mRNA输出在基因调控中是相互交织的。在这里，我们发现mRNA输出因子通常促进远端切割和聚腺苷化位点（PASs）的使用，导致长3' UTR异构体表达。通过关注输出受体NXF1，我们揭示了影响NXF1依赖性APA的几个基因特征，包括3' UTR大小、基因大小和AT含量。在本研究中，NXF1对APA的影响最大。令人惊讶的是，NXF1下调导致RNA聚合酶II （Pol II）在基因3'端积累，与其在APA调节中的作用相关。此外，NXF1与CFI-68合作，促进具有UGUA基序的长3' UTR异构体的核出口。总之，我们的工作揭示了NXF1在协调转录动力学，3‘端加工和长3’ UTR转录本的核输出中的重要作用，暗示NXF1是基因调控的纽带。
Alternative polyadenylation (APA) produces mRNA isoforms with different 3' UTR lengths. Previous studies indicated that 3' end processing and mRNA export are intertwined in gene regulation. Here, we show that mRNA export factors generally facilitate usage of distal cleavage and polyadenylation sites (PASs), leading to long 3' UTR isoform expression. By focusing on the export receptor NXF1, which exhibits the most potent effect on APA in this study, we reveal several gene features that impact NXF1-dependent APA, including 3' UTR size, gene size, and AT content. Surprisingly, NXF1 downregulation results in RNA polymerase II (Pol II) accumulation at the 3' end of genes, correlating with its role in APA regulation. Moreover, NXF1 cooperates with CFI-68 to facilitate nuclear export of long 3' UTR isoform with UGUA motifs. Together, our work reveals important roles of NXF1 in coordinating transcriptional dynamics, 3' end processing, and nuclear export of long 3' UTR transcripts, implicating NXF1 as a nexus of gene regulation.