title: The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with REF protein and acts as an RNA export factor.
abstract: ORF57 (MTA) one of the earliest Kaposi's sarcoma-associated herpesvirus (KSHV) regulatory proteins to be expressed is essential for virus lytic replication. A counterpart is present in every herpesvirus sequenced, indicating the importance of this signature viral protein and those examined act post-transcriptionally, affecting RNA splicing and transport. In KSHV-infected cells, ORF57 protein was present in a complex with REF (Aly) and TAP (NXF1), factors involved in cellular mRNA export. The ORF57 N-terminal region interacts with REF, whereas both N- and C-terminal domains of REF interact with ORF57. The ORF57-REF interaction was direct, whereas TAP appeared to be recruited via REF. In somatic cells, ectopically expressed ORF57 protein was shown to function as a CRM1-independent nuclear mRNA export factor, promoting export of mRNAs that are poor substrates for splicing. The gamma-herpesvirus ORF57 protein, and its alpha-1 herpesvirus ICP27 counterpart both export RNA through pathways involving REF and TAP proteins, although divergence of these herpesvirus subfamilies occurred some 180-210 million years ago. The TAP-mediated cellular mRNA export pathway is CRM1-independent. However, human immunodeficiency virus type 1 Rev protein-mediated RNA export, which is CRM1-dependent, was considerably inhibited by ORF57, suggesting that Rev and ORF57 compete for a common export component. These data strengthen arguments that TAP and CRM1 pathways converge in accessing similar components of the nuclear pore complex. We propose that ORF57-mediated RNA export may use different export factors to accommodate the KSHV-infected host cell environments, for example, in B-cells or endothelial cells and during the different phases of lytic virus replication.
authors.affiliation: Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Church Street, Glasgow, G11 5JR, Scotland, United Kingdom.
authors.forename: Poonam
authors.initials: P
authors.lastname: Malik
authors.forename: David J
authors.initials: DJ
authors.lastname: Blackbourn
authors.forename: J Barklie
authors.initials: JB
authors.lastname: Clements
mesh_terms: D021581:Active Transport, Cell Nucleus; D001692:Biological Transport; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D019143:Evolution, Molecular; D005982:Glutathione Transferase / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology*; D012260:Ribonucleases / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism* / Q000502:physiology*
chemical_list: C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D029543:Nucleocytoplasmic Transport Proteins; C415247:ORF57 protein, Herpesvirus saimiri; D010455:Peptides; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D012313:RNA; D004247:DNA; D005982:Glutathione Transferase; D012260:Ribonucleases