Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway.
The role of herpes simplex virus ICP27 protein in mRNA export is investigated by microinjection into Xenopus laevis oocytes. ICP27 dramatically stimulates the export of intronless viral mRNAs, but has no effect on the export of cellular mRNAs, U snRNAs or tRNA. Use of inhibitors shows, in contrast to previous suggestions, that ICP27 neither shuttles nor exports viral mRNA via the CRM1 pathway. Instead, ICP27-mediated viral RNA export requires REF and TAP/NXF1, factors involved in cellular mRNA export. ICP27 binds directly to REF and complexes containing ICP27, REF and TAP are found in vitro and in virally infected cells. A mutant ICP27 that does not interact with REF is inactive in viral mRNA export. We propose that ICP27 associates with viral mRNAs and recruits TAP/NXF1 via its interaction with REF proteins, allowing the otherwise inefficiently exported viral mRNAs to access the TAP-mediated export pathway. This represents a novel mechanism for export of viral mRNAs.
Koffa
M D
MD
Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK.
Clements
J B
JB
Izaurralde
E
E
Wadd
S
S
Wilson
S A
SA
Mattaj
I W
IW
Kuersten
S
S
D000818:Animals; D001692:Biological Transport; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D046911:Macromolecular Substances; D008845:Microinjections; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D009865:Oocytes; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
D005656:Fungal Proteins; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; C106898:MEX67 protein, S cerevisiae; D046911:Macromolecular Substances; C122111:NXF1 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; C092121:REF2 protein, S cerevisiae; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins