title: A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport.
abstract: Active nucleocytoplasmic transport of protein and RNA in eukaryotes depends on the Ran-GTPase system to regulate cargo-receptor interactions. Several viruses, including the RNA picornaviruses, encode factors that alter nuclear transport with the aim of suppressing synthesis of antiviral factors and promoting viral replication. Picornaviruses in the cardiovirus genus express a unique 67-aa Leader protein (L), known to alter the subcellular distribution of IFN regulatory proteins targeted to the nucleus. We report here that L binds directly to Ran and blocks nuclear export of new mRNAs. In Xenopus egg extracts, recombinant L also inhibits mitotic spindle assembly, a RanGTP function crucial to cell-cycle progression. We propose that L inhibits nucleocytoplasmic transport during infection by disrupting the RanGDP/GTP gradient. This inhibition triggers an efflux of nuclear proteins necessary for viral replication and causes IFN suppression. To our knowledge, L is the first viral picornaviral protein to interact directly with Ran and modulate the Ran-dependent nucleocytoplasmic pathway.
authors.affiliation: Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Porter
authors.forename: Yury A
authors.initials: YA
authors.lastname: Bochkov
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Albee
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiese
authors.forename: Ann C
authors.initials: AC
authors.lastname: Palmenberg
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010849:Picornaviridae / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D020931:ran GTP-Binding Protein