Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98.
Vesicular stomatitis virus matrix protein (VSV M) has been shown to inhibit both transcription and nucleocytoplasmic transport. We have isolated a mutant form of M, termed M(D), lacking both inhibitory activities. HeLa cells expressing M, but not M(D), accumulate polyadenylated RNAs within the nucleus. Concomitantly, a fraction of M, but not of the M(D) mutant, localizes at the nuclear rim. Additionally, the nucleoporin Nup98 specifically interacts with M but not with M(D). In Nup98(-/-) cells, both the levels of M at the nuclear envelope and its inhibitory effects on host cell-directed expression of reporter genes were significantly reduced. Together, our data demonstrate that VSV M inhibits host cell gene expression by targeting a nucleoporin and primarily blocking nuclear export.
von Kobbe C
European Molecular Biology Laboratory Meyerhofstrasse 1 D-69117, Heidelberg, Germany.
van Deursen JM
Rodrigues
J P
JP
Sitterlin
D
D
Bachi
A
A
Wu
X
X
Wilm
M
M
Carmo-Fonseca
M
M
Izaurralde
E
E
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D013379:Substrate Specificity; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C094460:M protein, Vesicular stomatitis virus; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; C093350:nuclear pore complex protein 98