The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human

The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human
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DOI:
10.1093/emboj/18.9.2593
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发表时间:
1999-05-04
期刊:
影响因子:
11.4
通讯作者:
Hurt, E
Hurt, E
中科院分区:
生物学1区
文献类型:
--
作者:
Katahira, J;Strässer, K;Hurt, E

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人TAP是酵母mRNA输出因子Mex 67 p的直向同源物。在哺乳动物细胞中,TAP具有优先的核内定位,但也可以在核孔处检测到并且在核和细胞质之间穿梭。TAP在体内直接与mRNA结合,因为它可以在HeLa细胞中与poly(A)(+)RNA UV交联。核孔蛋白CAN/Nup 214的FG-重复结构域和与NTF 2(与RanGDP相关的核转运因子)具有同源性的新的人15 kDa蛋白(p15)都直接结合TAP。当绿色荧光蛋白(GFP)标记的TAP和p15在酵母中表达时,它们定位于核孔。引人注目的是,人TAP和p15的共表达恢复了原本致命的mex 67::HIS 3/mtr 2::HIS 3双敲除菌株的生长。因此,人TAP-p15复合物可以在功能上取代酵母中的Mex 67 p-Mtr 2 p复合物,从而在核mRNA输出中发挥保守作用。
Human TAP is an orthologue of the yeast mRNA export factor Mex67p. In mammalian cells, TAP has a preferential intranuclear localization, but can also be detected at the nuclear pores and shuttles between the nucleus and the cytoplasm, TAP directly associates with mRNA in vivo, as it can be UV-crosslinked to poly(A)(+) RNA in HeLa cells. Both the FG-repeat domain of nucleoporin CAN/Nup214 and a novel human 15 kDa protein (p15) with homology to NTF2 (a nuclear transport factor which associates with RanGDP), directly bind to TAP. When green fluorescent protein (GFP)-tagged TAP and p15 are expressed in yeast, they localize to the nuclear pores. Strikingly, co-expression of human TAP and p15 restores growth of the otherwise lethal mex67::HIS3/mtr2::HIS3 double knockout strain, Thus, the human TAP-p15 complex can functionally replace the Mex67p-Mtr2p complex in yeast and thus performs a conserved role in nuclear mRNA export.