12月7日,，國際學(xué)術(shù)期刊Nucleic Acids Research在線發(fā)表了生化與細(xì)胞所程紅研究組題為“Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA”的研究論文，報(bào)道了Aly和 THO在mRNA出核復(fù)合物TREX組裝和招募中的作用。
mRNA出核轉(zhuǎn)運(yùn)是真核基因表達(dá)的一個(gè)關(guān)鍵步驟,，它與pre-mRNA的加工（包括5’加帽、剪接和3’加尾）密切偶聯(lián),，只有當(dāng)這些過程完成以后,，mRNA才能被轉(zhuǎn)運(yùn)出核翻譯成蛋白質(zhì)。mRNA出核復(fù)合物TREX主要由蛋白Aly,、UAP56,、Tex1和亞復(fù)合物THO組成。TREX伴隨剪接,、依賴與5’端帽結(jié)合蛋白CBP80的相互作用被招募到mRNA上,，并介導(dǎo)mRNA與其出核受體 TAP/P15間的相互作用。在酵母中,，TREX的組分是按照一定的順序依次被招募到mRNA上的,，然而人TREX是以相似的機(jī)制被招募，還是作為一個(gè)事先形成的復(fù)合體被招募還不清楚,。
博士研究生遲斌凱和王慶亮在程紅研究員的指導(dǎo)下,，系統(tǒng)研究了TREX各組分在TREX復(fù)合物組裝和募集到mRNA中的作用。該研究發(fā)現(xiàn)Aly,、UAP56和THO對(duì)于TREX的組裝缺一不可,。Aly和THO介導(dǎo)了TREX與CBP80的相互作用，并在TREX的募集過程中發(fā)揮必不可少的作用,。進(jìn)一步的研究表明,，與Aly和UAP56類似，THO在mRNA出核過程中也發(fā)揮了關(guān)鍵的作用,。以上結(jié)果提示TREX可能是作為一個(gè)整體被招募到mRNA上的,。 mRNA為何利用TREX這樣一個(gè)復(fù)雜的蛋白復(fù)合體來介導(dǎo)其與TAP/P15之間的聯(lián)系一直是一個(gè)不解之謎。該研究提示了一種有趣的可能性：不同的TREX組分有可能將TREX與不同的pre-mRNA加工過程聯(lián)系起來,，這樣,，只有當(dāng)所有的加工過程都結(jié)束時(shí),，TREX才能被有效地招募，mRNA也才能順利出核轉(zhuǎn)運(yùn)到細(xì)胞質(zhì)內(nèi)翻譯成蛋白質(zhì),。
該項(xiàng)工作得到國家科技部,、國家自然科學(xué)基金委、上海市科委以及中國科學(xué)院的經(jīng)費(fèi)資助,。(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.
