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First published online 29 September 2009
doi: 10.1242/jcs.055988

Journal of Cell Science 122, 3799-3809 (2009)
Published by The Company of Biologists 2009
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Research Article

RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage

Alfredo Castelló*, José M. Izquierdo, Ewelina Welnowska and Luis Carrasco{ddagger}

Centro de Biología Molecular `Severo Ochoa' (CSIC-UAM), C/Nicolás Cabrera, 1. Universidad Autónoma de Madrid. Cantoblanco, 28049 Madrid, Spain

{ddagger} Author for correspondence (lcarrasco{at}cbm.uam.es)

Accepted 12 August 2009

Cytopathic viruses have developed successful strategies to block or, at least, to attenuate host interference with their replication. Here, we have analyzed the effects of poliovirus 2A protease on RNA nuclear export. 2A protease interferes with trafficking of mRNAs, rRNAs and U snRNAs from the nucleus to the cytoplasm, without any apparent effect on tRNA transport. Traffic of newly produced mRNAs is more strongly affected than traffic of other mRNAs over-represented in the cytoplasm, such as mRNA encoding β-actin. Inhibition of RNA nuclear export in HeLa cells expressing 2A protease is concomitant with the cleavage of Nup98, Nup153, Nup62 and their subsequent subcellular redistribution. The expression of an inactive 2A protease failed to interfere with RNA nuclear export. In addition, other related proteases, such as poliovirus 3C or foot and mouth disease virus Lpro did not affect mRNA distribution or Nup98 integrity. Treatment of HeLa cells with interferon (IFN)-{gamma} increased the relative amount of Nup98. Under such conditions, the cleavage of Nup98 induced by 2A protease is partial, and thus IFN-{gamma} prevents the inhibition of RNA nuclear export. Taken together, these results are consistent with a specific proteolysis of Nup98 by 2A protease to prevent de novo mRNA traffic in poliovirus-infected cells.

Key words: 2A protease, RNA nuclear export, Nucleoporin, Interferon, Gene expression control


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