Chtop is a component of the dynamic TREX mRNA export complex

被引:90
作者
Chang, Chung-Te [1 ]
Hautbergue, Guillaume M. [1 ]
Walsh, Matthew J. [1 ]
Viphakone, Nicolas [1 ]
van Dijk, Thamar B. [2 ]
Philipsen, Sjaak [2 ]
Wilson, Stuart A. [1 ]
机构
[1] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England
[2] Erasmus MC, Dept Cell Biol, Rotterdam, Netherlands
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
ALY; C1ORF77; nuclear export; REF; TAP; GENOME-WIDE ANALYSIS; ARGININE METHYLATION; NUCLEAR EXPORT; FACTOR YRA1; RECRUITMENT; PROTEIN; DOMAIN; ATP; END; TRANSCRIPTION;
D O I
10.1038/emboj.2012.342
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
The TREX complex couples nuclear pre-mRNA processing with mRNA export and contains multiple protein components, including Uap56, Alyref, Cip29 and the multi-subunit THO complex. Here, we have identified Chtop as a novel TREX component. We show that both Chtop and Alyref activate the ATPase and RNA helicase activities of Uap56 and that Uap56 functions to recruit both Alyref and Chtop onto mRNA. As observed with the THO complex subunit Thoc5, Chtop binds to the NTF2-like domain of Nxf1, and this interaction requires arginine methylation of Chtop. Using RNAi, we show that co-knockdown of Alyref and Chtop results in a potent mRNA export block. Chtop binds to Uap56 in a mutually exclusive manner with Alyref, and Chtop binds to Nxf1 in a mutually exclusive manner with Thoc5. However, Chtop, Thoc5 and Nxf1 exist in a single complex in vivo. Together, our data indicate that TREX and Nxf1 undergo dynamic remodelling, driven by the ATPase cycle of Uap56 and post-translational modifications of Chtop.
引用
收藏
页码:473 / 486
页数:14
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