流感病毒NS1蛋白与细胞内切割和聚腺苷酸化特异性因子（CPSF）的30 kDa亚基相互作用，并抑制细胞前体mRNA的3'末端形成。

Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs.

作者信息

Nemeroff M E, Barabino S M, Li Y, Keller W, Krug R M

机构信息

Department of Molecular Biology and Biochemistry Rutgers University Piscataway, New Jersey 08854, USA.

出版信息

Mol Cell. 1998 Jun;1(7):991-1000. doi: 10.1016/s1097-2765(00)80099-4.

DOI:10.1016/s1097-2765(00)80099-4

PMID:9651582

Abstract

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.

摘要

甲型流感病毒NS1蛋白对含多聚腺苷酸（poly(A)）的mRNA核输出的抑制作用需要其效应结构域。在此，我们证明NS1效应结构域与细胞前体mRNA 3'端加工机制的关键组分CPSF的30 kDa细胞亚基发生功能性相互作用。在流感病毒感染的细胞中，NS1蛋白与CPSF 30 kDa存在物理关联。NS1蛋白在体外与30 kDa蛋白的结合可阻止CPSF与RNA底物结合，并抑制宿主前体mRNA的3'端切割和多聚腺苷酸化。NS1蛋白在体内也抑制3'端加工，未切割的前体mRNA保留在细胞核中。通过对前体mRNA 3'端加工的这种新型调控，NS1蛋白选择性地抑制细胞mRNA而非病毒mRNA的核输出。