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mRNA 输出受体 NXF1 协调转录动力学、可变多聚腺苷酸化和 mRNA 输出。

The mRNA Export Receptor NXF1 Coordinates Transcriptional Dynamics, Alternative Polyadenylation, and mRNA Export.

机构信息

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

出版信息

Mol Cell. 2019 Apr 4;74(1):118-131.e7. doi: 10.1016/j.molcel.2019.01.026. Epub 2019 Feb 25.

DOI:10.1016/j.molcel.2019.01.026
PMID:30819645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6450743/
Abstract

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.

摘要

可变多聚腺苷酸化 (APA) 产生具有不同 3'UTR 长度的 mRNA 异构体。先前的研究表明，3'末端加工和 mRNA 输出在基因调控中交织在一起。在这里，我们表明，mRNA 输出因子通常促进使用远端切割和多聚腺苷酸化位点 (PAS)，导致长 3'UTR 异构体的表达。通过专注于出口受体 NXF1，它在本研究中对 APA 表现出最有效的作用，我们揭示了几个影响 NXF1 依赖的 APA 的基因特征，包括 3'UTR 大小、基因大小和 AT 含量。令人惊讶的是，NXF1 的下调导致 RNA 聚合酶 II (Pol II) 在基因的 3'末端积累，这与其在 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 异构体的核输出。总之，我们的工作揭示了 NXF1 在协调转录动力学、3'末端加工和长 3'UTR 转录物的核输出方面的重要作用，表明 NXF1 是基因调控的枢纽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/fc9a4cfea644/nihms-1519336-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/f2ef77f827ea/nihms-1519336-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/f9c8a352a355/nihms-1519336-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/bd357f58bbb1/nihms-1519336-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/022c6fde10ec/nihms-1519336-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/6ffba19ee036/nihms-1519336-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/fc9a4cfea644/nihms-1519336-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/f2ef77f827ea/nihms-1519336-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/e0ebe0889c26/nihms-1519336-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/f9c8a352a355/nihms-1519336-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/bd357f58bbb1/nihms-1519336-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/022c6fde10ec/nihms-1519336-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/6ffba19ee036/nihms-1519336-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2797/6450743/fc9a4cfea644/nihms-1519336-f0008.jpg

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