The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with REF protein and acts as an RNA export factor

Malik, P., Blackbourn, D.J. and Clements, J.B. (2004) The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with REF protein and acts as an RNA export factor. Journal of Biological Chemistry, 279, pp. 33001-33011. (doi: 10.1074/jbc.M313008200)

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 γ-herpesvirus ORF57 protein, and its α-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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: UNSPECIFIED
• Authors: Malik, P., Blackbourn, D.J., and Clements, J.B.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J Biol Chem.
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X