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PMID: 15537388 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway.

The Biochemical journal ·Vol. 387 ·No. Pt 2 ·2005-04-15 ·Pages 295-308

Williams BJ, Boyne JR, Goodwin DJ, Roaden L, Hautbergue GM, Wilson SA, Whitehouse A

Abstract

HVS (herpesvirus saimiri) is the prototype gamma-2 herpesvirus. This is a subfamily of herpesviruses gaining importance since the identification of the first human gamma-2 herpesvirus, Kaposi's sarcoma-associated herpesvirus. The HVS ORF 57 (open reading frame 57) protein is a multifunctional transregulatory protein homologous with genes identified in all classes of herpesviruses. Recent work has demonstrated that ORF 57 has the ability to bind viral RNA, shuttles between the nucleus and cytoplasm and promotes the nuclear export of viral transcripts. In the present study, we show that ORF 57 shuttles between the nucleus and cytoplasm in a CRM-1 (chromosomal region maintenance 1)-independent manner. ORF 57 interacts with the mRNA export factor REF (RNA export factor) and two other components of the exon junction complex, Y14 and Magoh. The association of ORF 57 with REF stimulates recruitment of the cellular mRNA export factor TAP (Tip-associated protein), and HVS infection triggers the relocalization of REF and TAP from the nuclear speckles to several large clumps within the cell. Using a dominant-negative form of TAP and RNA interference to deplete TAP, we show that it is essential for bulk mRNA export in mammalian cells and is required for ORF 57-mediated viral RNA export. Furthermore, we show that the disruption of TAP reduces viral replication. These results indicate that HVS utilizes ORF 57 to recruit components of the exon junction complex and subsequently TAP to promote viral RNA export through the cellular mRNA export pathway.

MeSH Terms
Active Transport, Cell Nucleus/physiology Animals COS Cells Cell Nucleus/metabolism Chlorocebus aethiops Herpesvirus 2, Saimiriine/physiology Karyopherins/metabolism Nuclear Envelope/metabolism Nucleocytoplasmic Transport Proteins/physiology RNA Transport/physiology RNA, Messenger/metabolism RNA, Viral/metabolism Receptors, Cytoplasmic and Nuclear/metabolism Repressor Proteins/physiology Trans-Activators/physiology Two-Hybrid System Techniques Viral Proteins/physiology
Chemicals
Karyopherins Nucleocytoplasmic Transport Proteins ORF57 protein, Herpesvirus saimiri RNA, Messenger RNA, Viral Receptors, Cytoplasmic and Nuclear Repressor Proteins Trans-Activators Viral Proteins exportin 1 protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Williams Ben J L
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK.
Boyne James R
Goodwin Delyth J
Roaden Louise
Hautbergue Guillaume M
Wilson Stuart A
Whitehouse Adrian
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20041223
Published
2005-04-15
Pages
295-308
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1134957
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BBS/B/03475 · United Kingdom
External Links
PubMed source DOI: 10.1042/BJ20041223 PMC Full Text View journal details
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