RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage.
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 beta-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 L(pro) 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.
Centro de Biología Molecular, Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1 Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Alfredo
A
Castelló
José M
JM
Izquierdo
Ewelina
E
Welnowska
Luis
L
Carrasco
D000086042:3C Viral Proteases; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D026723:Polyadenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D034443:RNA Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012342:RNA, Small Nuclear; D014764:Viral Proteins; D007371:Interferon-gamma; D012343:RNA, Transfer; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C057400:picornain 2A, Picornavirus