Targeting and function in mRNA export of nuclear pore complex protein Nup153

Targeting and function in mRNA export of nuclear pore complex protein Nup153
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DOI:
10.1083/jcb.134.5.1141
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发表时间:
1996-09-01
影响因子:
7.8
通讯作者:
Burke, B
Burke, B
中科院分区:
生物学1区
文献类型:
--
作者:
Bastos, R;Lin, A;Burke, B

文献摘要

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Nup 153是一个大的(153 kD)O-连接糖蛋白,它是位于核孔复合物的核质面上的篮状结构的组分。该蛋白质具有三联结构,由两侧为大的(60-70 kD)NH 2-和COOH-末端结构域的锌指结构域组成。当全长人Nup 153在BHK细胞中表达时,其在核膜的核质面适当地积累。Nup 153的靶向信息存在于NH 2-末端结构域,因为该分子的该区域可以将通常的细胞质蛋白丙酮酸激酶引导至核孔复合物的核面。Nup 153的过表达导致核poly(A)(+)RNA的显著积累,表明RNA从核输出的抑制。这不是由于核质转运的普遍下降或核孔复合物的闭塞或损失,因为核蛋白输入不受影响。虽然发现某些Nup 153构建体的过表达导致不寻常的核内膜阵列的形成,但这种结构表型与对poly(A)(+)RNA分布的影响无关。然而,RNA运输缺陷依赖于Nup 153 COOH末端结构域,该结构域包含大部分XFXFG重复序列。有人提出,这一地区的Nup 153,位于核篮的远端环内,代表了一个对接站点的mRNA分子退出细胞核。
Nup153 is a large (153 kD) O-linked glycoprotein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes. This protein exhibits a tripartite structure consisting of a zinc finger domain flanked by large (60-70 kD) NH2- and COOH-terminal domains. When full-length human Nup153 is expressed in BHK cells, it accumulates appropriately at the nucleoplasmic face of the nuclear envelope. Targeting information for Nup153 resides in the NH2-terminal domain since this region of the molecule can direct an ordinarily cytoplasmic protein, pyruvate kinase, to the nuclear face of the nuclear pore complex. Overexpression of Nup153 results in the dramatic accumulation of nuclear poly (A)(+) RNA, suggesting an inhibition of RNA export from the nucleus. This is not due to a general decline in nucleocytoplasmic transport or to occlusion or loss of nuclear pore complexes since nuclear protein import is unaffected. While overexpression of certain Nup153 constructs was found to result in the formation of unusual intranuclear membrane arrays, this structural phenotype could not be correlated with the effects on poly (A)(+) RNA distribution, The RNA trafficking defect was, however, dependent upon the Nup153 COOH-terminal domain which contains most of the XFXFG repeats. It is proposed that this region of Nup153, lying within the distal ring of the nuclear basket, represents a docking site for mRNA molecules exiting the nucleus.