12月7日,国际学术期刊Nucleic Acids Research在线发表了生化与细胞所程红研究组题为“Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA”的研究论文,报道了Aly和 THO在mRNA出核复合物TREX组装和招募中的作用。
mRNA出核转运是真核基因表达的一个关键步骤,它与pre-mRNA的加工(包括5’加帽、剪接和3’加尾)密切偶联,只有当这些过程完成以后,mRNA才能被转运出核翻译成蛋白质。mRNA出核复合物TREX主要由蛋白Aly、UAP56、Tex1和亚复合物THO组成。TREX伴随剪接、依赖与5’端帽结合蛋白CBP80的相互作用被招募到mRNA上,并介导mRNA与其出核受体 TAP/P15间的相互作用。在酵母中,TREX的组分是按照一定的顺序依次被招募到mRNA上的,然而人TREX是以相似的机制被招募,还是作为一个事先形成的复合体被招募还不清楚。
博士研究生迟斌凯和王庆亮在程红研究员的指导下,系统研究了TREX各组分在TREX复合物组装和募集到mRNA中的作用。该研究发现Aly、UAP56和THO对于TREX的组装缺一不可。Aly和THO介导了TREX与CBP80的相互作用,并在TREX的募集过程中发挥必不可少的作用。进一步的研究表明,与Aly和UAP56类似,THO在mRNA出核过程中也发挥了关键的作用。以上结果提示TREX可能是作为一个整体被招募到mRNA上的。 mRNA为何利用TREX这样一个复杂的蛋白复合体来介导其与TAP/P15之间的联系一直是一个不解之谜。该研究提示了一种有趣的可能性:不同的TREX组分有可能将TREX与不同的pre-mRNA加工过程联系起来,这样,只有当所有的加工过程都结束时,TREX才能被有效地招募,mRNA也才能顺利出核转运到细胞质内翻译成蛋白质。
该项工作得到国家科技部、国家自然科学基金委、上海市科委以及中国科学院的经费资助。(生物谷Bioon.com)
doi: 10.1093/nar/gks1188
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Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA
Binkai Chi, Qingliang Wang, Guifen Wu, Ming Tan, Lantian Wang, Min Shi, Xingya Chang and Hong Cheng*
The mRNA export complex TREX (TREX) is known to contain Aly, UAP56, Tex1 and the THO complex, among which UAP56 is required for TREX assembly. Here, we systematically investigated the role of each human TREX component in TREX assembly and its association with the mRNA. We found that Tex1 is essentially a subunit of the THO complex. Aly, THO and UAP56 are all required for assembly of TREX, in which Aly directly interacts with THO subunits Thoc2 and Thoc5. Both Aly and THO function in linking UAP56 to the cap-binding protein CBP80. Interestingly, association of UAP56 with the spliced mRNA, but not with the pre-mRNA, requires Aly and THO. Unexpectedly, we found that Aly and THO require each other to associate with the spliced mRNA. Consistent with these biochemical results, similar to Aly and UAP56, THO plays critical roles in mRNA export. Together, we propose that Aly, THO and UAP56 form a highly integrated unit to associate with the spliced mRNA and function in mRNA export.