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 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-gamma, 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.
Faria
Paula A
PA
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA.
Chakraborty
Papia
P
Levay
Agata
A
Barber
Glen N
GN
Ezelle
Heather J
HJ
Enninga
Jost
J
Arana
Carlos
C
van Deursen
Jan
J
Fontoura
Beatriz M A
BM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
D034521:Nuclear Matrix-Associated Proteins; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490522:RAE1 protein, human; D012333:RNA, Messenger; C490521:Rae1 protein, mouse; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C093350:nuclear pore complex protein 98