Faria Paula A, Chakraborty Papia, Levay Agata, Barber Glen N, Ezelle Heather J, Enninga Jost, Arana Carlos, van Deursen Jan, Fontoura Beatriz M A
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA.
Mol Cell. 2005 Jan 7;17(1):93-102. doi: 10.1016/j.molcel.2004.11.023.
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.
干扰核质运输是某些病毒用来损害宿主细胞功能的一种策略。虽然已经表明水疱性口炎病毒（VSV）的基质（M）蛋白会抑制宿主细胞mRNA的核输出，但其潜在机制尚未完全明确。在此我们表明，VSV M蛋白与mRNA输出因子Rae1/mrnp41结合。在与Rae1结合方面存在缺陷的M蛋白突变体无法抑制mRNA的核输出。我们进一步表明，Rae1表达的增加可完全逆转由M蛋白或病毒感染后所诱导的mRNA输出抑制。我们发现Rae1是由γ干扰素诱导产生的，γ干扰素是一种在针对病毒（如水疱性口炎病毒）的免疫反应中起关键作用的细胞因子。因此，这些结果表明，VSV M蛋白通过破坏Rae1的功能来阻断mRNA输出，而Rae1表达的诱导可使其恢复。
