Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs
Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs
复制标题
DOI：
10.1016/s1097-2765(00)80099-4
复制
发表时间：
1998-06-01
期刊：
影响因子：
16
通讯作者：
Krug, RM
中科院分区：
文献类型：
--
作者：
Nemeroff, ME;Barabino, SML;Krug, RM
由甲型流感病毒NS1蛋白引起的含poly（A）的mRNA的核输出的抑制需要其效应结构域。在这里，我们证明了NS1效应结构域功能上与细胞30 kDa亚基的CPSF，细胞前mRNA的3'端加工机制的重要组成部分相互作用。在流感病毒感染的细胞中，NS1蛋白与CPSF 30 kDa物理结合。NS1蛋白与30 kDa蛋白的体外结合阻止了CPSF与RNA底物的结合，并抑制了宿主前体mRNA的3'端切割和多腺苷酸化。NS1蛋白还抑制体内的3'末端加工，并且未切割的前mRNA保留在细胞核中。通过这种对前mRNA 3'端加工的新调节，NS1蛋白选择性地抑制细胞而非病毒mRNA的核输出。
Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector domain. Here, we demonstrate that the NS1 effector domain functionally interacts with the cellular 30 kDa subunit of CPSF, an essential component of the 3' end processing machinery of cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is physically associated with CPSF 30 kDa. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs. The NS1 protein also inhibits 3' end processing in vivo, and the uncleaved pre-mRNA remains in the nucleus. Via this novel regulation of pre-mRNA 3' end processing, the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs.