Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA.
Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA.
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DOI：
10.1371/journal.pone.0029921
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Nandicoori VK
中科院分区：
文献类型：
--
作者：
Rajanala K;Nandicoori VK
核孔蛋白Tpr是核孔复合物（NPC）的一个组成部分，它只定位于核内丝。Tpr作为NPC核期的支架元件，在有丝分裂纺锤体检查点信号传导中发挥作用。Mason Pfizer猴病毒含内含子mRNA的输出受细胞蛋白与顺式组成转运元件（CTE）的直接相互作用调控。在哺乳动物细胞中，Gag/Pol-CTE报告结构的转运效率不高，这表明存在一种保留这种未剪接RNA的调节机制。在这里，我们报道了哺乳动物细胞中Tpr的敲低导致细胞质中Gag蛋白（p24）水平的急剧提高，这是由siRNA抗性Tpr拯救的。Tpr在保留未剪接RNA中的作用独立于Sam68和Tap/Nxf1蛋白的功能，据报道，Sam68和Tap/Nxf1蛋白促进CTE依赖的输出。此外，我们研究了核孔蛋白在核胞质转运中调节非剪接RNA输出的可能作用。结果表明，Nup153 （NPC锚定Tpr所需的核孔蛋白）的缺失对非剪接RNA的输出起调节作用，而其他含有FG重复序列的核孔蛋白的缺失并未改变非剪接RNA的输出。结果表明，Tpr和Nup153都调节未剪接RNA的输出，它们很可能通过相同的途径发挥作用。重要的是，我们发现Tpr定位到NPC对于Tpr介导的非剪接RNA输出调控是必要的。总的来说，这些数据表明，核孔复合物中Tpr的核周定位对于通过直接或间接参与异常mRNA转录物的加工和降解来调节含内含子的mRNA输出至关重要。
Nucleoporin Tpr is a component of the nuclear pore complex (NPC) that localizes exclusively to intranuclear filaments. Tpr functions as a scaffolding element in the nuclear phase of the NPC and plays a role in mitotic spindle checkpoint signalling. Export of intron-containing mRNA in Mason Pfizer Monkey Virus is regulated by direct interaction of cellular proteins with the cis-acting Constitutive Transport Element (CTE). In mammalian cells, the transport of Gag/Pol-CTE reporter construct is not very efficient, suggesting a regulatory mechanism to retain this unspliced RNA. Here we report that the knockdown of Tpr in mammalian cells leads to a drastic enhancement in the levels of Gag proteins (p24) in the cytoplasm, which is rescued by siRNA resistant Tpr. Tpr's role in the retention of unspliced RNA is independent of the functions of Sam68 and Tap/Nxf1 proteins, which are reported to promote CTE dependent export. Further, we investigated the possible role for nucleoporins that are known to function in nucleocytoplasmic transport in modulating unspliced RNA export. Results show that depletion of Nup153, a nucleoporin required for NPC anchoring of Tpr, plays a role in regulating the export, while depletion of other FG repeat-containing nucleoporins did not alter the unspliced RNA export. Results suggest that Tpr and Nup153 both regulate the export of unspliced RNA and they are most likely functioning through the same pathway. Importantly, we find that localization of Tpr to the NPC is necessary for Tpr mediated regulation of unspliced RNA export. Collectively, the data indicates that perinuclear localization of Tpr at the nucleopore complex is crucial for regulating intron containing mRNA export by directly or indirectly participating in the processing and degradation of aberrant mRNA transcripts.
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