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

被引:43
作者
Chen, Suli [1 ]
Wang, Ruijia [2 ]
Zheng, Dinghai [2 ]
Zhang, Heng [1 ]
Chang, Xingya [1 ]
Wang, Ke [1 ]
Li, Wencheng [2 ]
Fan, Jing [1 ]
Tian, Bin [2 ]
Cheng, Hong [1 ]
机构
[1] Univ Chinese Acad Sci, Shanghai Key Lab Mol Androl, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, Shanghai 200031, Peoples R China
[2] Rutgers New Jersey Med Sch, Dept Microbiol Biochem & Mol Genet, Newark, NJ 07103 USA
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
NUCLEAR-PORE COMPLEX; COTRANSCRIPTIONAL RECRUITMENT; GENE-EXPRESSION; READ ALIGNMENT; POLYMERASE-II; FACTOR YRA1; CLEAVAGE; END; PROTEINS; LOCALIZATION;
D O I
10.1016/j.molcel.2019.01.026
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:118 / +
页数:21
相关论文
共 67 条
[1]   Differential expression analysis for sequence count data [J].
Anders, Simon ;
Huber, Wolfgang .
GENOME BIOLOGY, 2010, 11 (10)
[2]   HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].
Anders, Simon ;
Pyl, Paul Theodor ;
Huber, Wolfgang .
BIOINFORMATICS, 2015, 31 (02) :166-169
[3]   The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates [J].
Bachi, A ;
Braun, IC ;
Rodrigues, JP ;
Panté, N ;
Ribbeck, K ;
Von Kobbe, C ;
Kutay, U ;
Wilm, M ;
Görlich, D ;
Carmo-Fonseca, M ;
Izaurralde, E .
RNA, 2000, 6 (01) :136-158
[4]   Mechanisms of mRNA export [J].
Bjork, Petra ;
Wieslander, Lars .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2014, 32 :47-54
[5]   Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization [J].
Casolari, JM ;
Brown, CR ;
Komili, S ;
West, J ;
Hieronymus, H ;
Silver, PA .
CELL, 2004, 117 (04) :427-439
[6]   Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA [J].
Chi, Binkai ;
Wang, Qingliang ;
Wu, Guifen ;
Tan, Ming ;
Wang, Lantian ;
Shi, Min ;
Chang, Xingya ;
Cheng, Hong .
NUCLEIC ACIDS RESEARCH, 2013, 41 (02) :1294-1306
[7]   Nuclear pore complexes as hubs for gene regulation [J].
D'Angelo, Maximiliano A. .
NUCLEUS, 2018, 9 (01) :142-148
[8]   Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to nuclear pore anchoring of activated genes [J].
Dieppois, Guennaelle ;
Iglesias, Nahid ;
Stutz, Francoise .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (21) :7858-7870
[9]   Landscape of transcription in human cells [J].
Djebali, Sarah ;
Davis, Carrie A. ;
Merkel, Angelika ;
Dobin, Alex ;
Lassmann, Timo ;
Mortazavi, Ali ;
Tanzer, Andrea ;
Lagarde, Julien ;
Lin, Wei ;
Schlesinger, Felix ;
Xue, Chenghai ;
Marinov, Georgi K. ;
Khatun, Jainab ;
Williams, Brian A. ;
Zaleski, Chris ;
Rozowsky, Joel ;
Roeder, Maik ;
Kokocinski, Felix ;
Abdelhamid, Rehab F. ;
Alioto, Tyler ;
Antoshechkin, Igor ;
Baer, Michael T. ;
Bar, Nadav S. ;
Batut, Philippe ;
Bell, Kimberly ;
Bell, Ian ;
Chakrabortty, Sudipto ;
Chen, Xian ;
Chrast, Jacqueline ;
Curado, Joao ;
Derrien, Thomas ;
Drenkow, Jorg ;
Dumais, Erica ;
Dumais, Jacqueline ;
Duttagupta, Radha ;
Falconnet, Emilie ;
Fastuca, Meagan ;
Fejes-Toth, Kata ;
Ferreira, Pedro ;
Foissac, Sylvain ;
Fullwood, Melissa J. ;
Gao, Hui ;
Gonzalez, David ;
Gordon, Assaf ;
Gunawardena, Harsha ;
Howald, Cedric ;
Jha, Sonali ;
Johnson, Rory ;
Kapranov, Philipp ;
King, Brandon .
NATURE, 2012, 489 (7414) :101-108
[10]   THOC5 controls 3′end- processing of immediate early genes via interaction with polyadenylation specific factor 100 (CPSF100) [J].
Doan Duy Hai Tran ;
Saran, Shashank ;
Williamson, Andrew J. K. ;
Pierce, Andrew ;
Dittrich-Breiholz, Oliver ;
Wiehlmann, Lutz ;
Koch, Alexandra ;
Whetton, Anthony D. ;
Tamura, Teruko .
NUCLEIC ACIDS RESEARCH, 2014, 42 (19) :12249-12260