Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs.
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.
Nemeroff
M E
ME
Department of Molecular Biology and Biochemistry Rutgers University Piscataway, New Jersey 08854, USA.
Barabino
S M
SM
Li
Y
Y
Keller
W
W
Krug
R M
RM
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D002461:Cell Line, Transformed; D005057:Eukaryotic Cells / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011523:Protoplasts / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D017361:Viral Nonstructural Proteins / Q000378:metabolism* / Q000494:pharmacology; D039221:mRNA Cleavage and Polyadenylation Factors
C085820:INS1 protein, influenza virus; D009687:Nuclear Proteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D011061:Poly A