The prototype γ-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway
| Autor: | Delyth J. Goodwin, Stuart A. Wilson, Adrian Whitehouse, Ben J. L. Williams, James R. Boyne, Guillaume M. Hautbergue, Louise Roaden |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Nucleocytoplasmic Transport Proteins
Nuclear Envelope viruses Active Transport Cell Nucleus Receptors Cytoplasmic and Nuclear Biology Karyopherins Biochemistry RNA Transport Herpesvirus 2 Saimiriine Viral Proteins RNA interference Two-Hybrid System Techniques Chlorocebus aethiops medicine Animals RNA Messenger Nuclear export signal Molecular Biology Cell Nucleus Messenger RNA RNA Cell Biology Molecular biology Repressor Proteins Open reading frame Cell nucleus medicine.anatomical_structure Viral replication COS Cells Trans-Activators Exon junction complex RNA Viral Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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