Severe acute respiratory syndrome coronavirus nonstructural protein 1 (nsp1) is a key factor in virus-induced down-regulation of host gene expression. In infected cells, nsp1 engages in a multipronged mechanism to inhibit host gene expression by binding to the 40S ribosome to block the assembly of translationally competent ribosome, and then inducing endonucleolytic cleavage and the degradation of host mRNAs. Here, we report a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts the nuclear-cytoplasmic transport of biomolecules. We identified members of the nuclear pore complex from the nsp1-associated protein assembly and found that the expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation, while the nuclear lamina remains unperturbed. Consistent with its role in host shutoff, nsp1 alters the nuclear-cytoplasmic distribution of an RNA binding protein, nucleolin. Our results suggest that nsp1, alone, can regulate multiple steps of gene expression including nuclear-cytoplasmic transport.

中文翻译：

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SARS冠状病毒蛋白nsp1破坏Nup93从核孔复合物中的定位。

严重的急性呼吸系统综合症冠状病毒非结构蛋白1（nsp1）是病毒诱导的宿主基因表达下调的关键因素。在受感染的细胞中，nsp1通过结合40S核糖体以阻止翻译感受态核糖体的装配，然后诱导核酸内切酶裂解和宿主mRNA的降解，从而参与了抑制宿主基因表达的多重机制。在这里，我们报告一个以前未被发现的机制，nsp1通过该机制利用核孔复合体并破坏生物分子的核质运输。我们从nsp1相关蛋白装配中鉴定了核孔复合体的成员，发现HEK细胞中nsp1的表达破坏了Nup93在核膜周围的定位，而没有触发蛋白水解降解，而核薄层保持不动。与它在宿主关闭中的作用一致，nsp1改变了RNA结合蛋白核仁素的核质分布。我们的研究结果表明，nsp1本身可以调节基因表达的多个步骤，包括核质运输。