VSV Disrupts the Rae1/mrnp41 mRNA Nuclear Export Pathway

Interference with nucleocytoplasmic transport is a strategy employed by certain viruses to compromise host cellular function. While it has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs, the underlying mechanism has not been...

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Bibliographic Details
Published in:Molecular cell 2005-01, Vol.17 (1), p.93-102
Main Authors: Faria, Paula A., Chakraborty, Papia, Levay, Agata, Barber, Glen N., Ezelle, Heather J., Enninga, Jost, Arana, Carlos, van Deursen, Jan, Fontoura, Beatriz M.A.
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Animals
Cell Line
HeLa Cells
Humans
In Vitro Techniques
Mice
Nuclear Matrix-Associated Proteins - genetics
Nuclear Matrix-Associated Proteins - metabolism
Nuclear Pore Complex Proteins - genetics
Nuclear Pore Complex Proteins - metabolism
Nucleocytoplasmic Transport Proteins - genetics
Nucleocytoplasmic Transport Proteins - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Vesicular stomatitis Indiana virus - genetics
Vesicular stomatitis Indiana virus - pathogenicity
Vesicular stomatitis Indiana virus - physiology
Vesicular stomatitis virus
Viral Matrix Proteins - genetics
Viral Matrix Proteins - physiology
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Summary:Interference with nucleocytoplasmic transport is a strategy employed by certain viruses to compromise host cellular function. While it has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs, the underlying mechanism has not been fully established. Here we show that VSV M protein binds the mRNA export factor Rae1/mrnp41. A mutant of M protein defective in Rae1 binding is unable to inhibit mRNA nuclear export. We further show that increased expression of Rae1 fully reverts the inhibition of mRNA export induced by M protein or following virus infection. We found that Rae1 is induced by interferon-γ, a cytokine that plays a critical role in the immune response to viruses, such as VSV. Thus, these results demonstrate that VSV M protein blocks mRNA export by disrupting Rae1 function, which can be reverted by induction of Rae1 expression.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2004.11.023