Title

mRNA nuclear export pathway disrupted by the vesicular stomatitis virus

Date of Award

2005

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Molecular and Cellular Pharmacology

First Committee Member

Beatriz M. A. Fontoura, Committee Chair

Abstract

All transport into and out of the nucleus occurs through the nuclear pore complexes (NPC). Interference with nucleocytoplasmic transport is a strategy employed by certain viruses to compromise host cellular function. It has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs by interfering with the function of a dynamic nucleoporin termed Nup98. Nup98 is involved in nuclear traffic of proteins as well as RNAs. The underlying mechanism by which VSV M protein inhibits mRNA export has not been fully established. Here we show that VSV M protein interacts with the mRNA export factor Rae1/mrnp41, which is an interacting partner of Nup98. 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 alpha/beta, as well as by interferon-gamma, which are cytokines that play critical roles 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.

Keywords

Biology, Molecular; Health Sciences, Pharmacology; Health Sciences, Immunology

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3198722