State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nucleic Acids Res. 2013 Jan;41(2):1294-306. doi: 10.1093/nar/gks1188. Epub 2012 Dec 7.
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.
mRNA 输出复合物 TREX(TREX)已知包含 Aly、UAP56、Tex1 和 THO 复合物,其中 UAP56 是 TREX 组装所必需的。在这里,我们系统地研究了人类 TREX 复合物的每个成分在 TREX 组装及其与 mRNA 关联中的作用。我们发现 Tex1 本质上是 THO 复合物的一个亚基。Aly、THO 和 UAP56 都需要组装 TREX,其中 Aly 直接与 THO 亚基 Thoc2 和 Thoc5 相互作用。Aly 和 THO 都参与将 UAP56 连接到帽结合蛋白 CBP80。有趣的是,UAP56 与剪接的 mRNA 结合,而不是与前体 mRNA 结合,需要 Aly 和 THO。出乎意料的是,我们发现 Aly 和 THO 需要彼此结合才能与剪接的 mRNA 结合。与这些生化结果一致,THO 与 Aly 和 UAP56 相似,在 mRNA 输出中发挥关键作用。总之,我们提出 Aly、THO 和 UAP56 形成一个高度集成的单元与剪接的 mRNA 结合并在 mRNA 输出中发挥作用。