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

Ben J L Williams, James R. Boyne, Delyth J. Goodwin, Louise Roaden, Guillaume M. Hautbergue, Stuart A. Wilson, Adrian Whitehouse

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

HVS (herpesvirus saimiri) is the prototype γ-2 herpesvirus. This is a subfamily of herpesviruses gaining importance since the identification of the first human γ-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.

LanguageEnglish
Pages295-308
Number of pages14
JournalBiochemical Journal
Volume387
Issue number2
DOIs
Publication statusPublished - 15 Apr 2005
Externally publishedYes

Fingerprint

Herpesviridae
Viral RNA
Open Reading Frames
Saimiriine Herpesvirus 2
Messenger RNA
RNA
Proteins
Exons
Cytoplasm
Viral Proteins
Speckle
Nuclear Proteins
Herpesviridae Infections
Human Herpesvirus 8
Human Herpesvirus 2
Cell Nucleus Active Transport
RNA Interference
Genes
Cells
Maintenance

Cite this

Williams, Ben J L ; Boyne, James R. ; Goodwin, Delyth J. ; Roaden, Louise ; Hautbergue, Guillaume M. ; Wilson, Stuart A. ; Whitehouse, Adrian. / The prototype γ-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway. In: Biochemical Journal. 2005 ; Vol. 387, No. 2. pp. 295-308.
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The prototype γ-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway. / Williams, Ben J L; Boyne, James R.; Goodwin, Delyth J.; Roaden, Louise; Hautbergue, Guillaume M.; Wilson, Stuart A.; Whitehouse, Adrian.

In: Biochemical Journal, Vol. 387, No. 2, 15.04.2005, p. 295-308.

Research output: Contribution to journalArticle

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T1 - The prototype γ-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway

AU - Williams, Ben J L

AU - Boyne, James R.

AU - Goodwin, Delyth J.

AU - Roaden, Louise

AU - Hautbergue, Guillaume M.

AU - Wilson, Stuart A.

AU - Whitehouse, Adrian

PY - 2005/4/15

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N2 - HVS (herpesvirus saimiri) is the prototype γ-2 herpesvirus. This is a subfamily of herpesviruses gaining importance since the identification of the first human γ-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.

AB - HVS (herpesvirus saimiri) is the prototype γ-2 herpesvirus. This is a subfamily of herpesviruses gaining importance since the identification of the first human γ-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.

KW - Chromosomal region maintenance 1 (CRM-1)

KW - Exon junction complex

KW - Herpesvirus

KW - MRNA export

KW - Open reading frame 57 (ORF 57)

KW - Tip-associated protein (TAP)

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DO - 10.1042/BJ20041223

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T2 - Biochemical Journal

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SN - 0264-6021

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