1887

Abstract

The UL69 protein of human cytomegalovirus is a multifunctional regulatory protein that has counterparts in all herpesviruses. Some of these proteins have been shown to function primarily at the post-transcriptional level in promoting nuclear export of viral transcripts. Consistently, this group has reported recently that pUL69 is an RNA-binding, nucleocytoplasmic shuttling protein that facilitates the cytoplasmic accumulation of unspliced mRNA via its interaction with the cellular mRNA export factor UAP56. Evidence has been presented to suggest that some of the pUL69 homologues self-interact and function as multimers. Herein, the possibility of pUL69 self-association was examined and it has been demonstrated that pUL69 can interact with itself and in order to form high-molecular-mass complexes. The self-interaction domain within pUL69 was mapped to a central domain of this viral protein that is conserved within the homologous proteins of other herpesviruses, suggesting that multimerization is a conserved feature of this protein family.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82480-0
2007-02-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/2/405.html?itemId=/content/journal/jgv/10.1099/vir.0.82480-0&mimeType=html&fmt=ahah

References

  1. Boyne J. R., Whitehouse A. 2006; γ -2 Herpes virus post-transcriptional gene regulation. Clin Microbiol Infect 12:110–117 [CrossRef]
    [Google Scholar]
  2. Chen I. H., Li L., Silva L., Sandri-Goldin R. M. 2005; ICP27 recruits Aly/REF but not TAP/NXF1 to herpes simplex virus type 1 transcription sites although TAP/NXF1 is required for ICP27 export. J Virol 79:3949–3961 [CrossRef]
    [Google Scholar]
  3. Cullen B. R. 2003; Nuclear mRNA export: insights from virology. Trends Biochem Sci 28:419–424 [CrossRef]
    [Google Scholar]
  4. Hiriart E., Bardouillet L., Manet E., Gruffat H., Penin F., Montserret R., Farjot G., Sergeant A. 2003; A region of the Epstein–Barr virus (EBV) mRNA export factor EB2 containing an arginine-rich motif mediates direct binding to RNA. J Biol Chem 278:37790–37798 [CrossRef]
    [Google Scholar]
  5. Jones D. T. 1999; Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292:195–202 [CrossRef]
    [Google Scholar]
  6. Lischka P., Stamminger T. 2006; Regulation of viral mRNA export from the nucleus. In Cytomegaloviruses: Molecular Biology and Immunology pp  185–204 Edited by Reddehase M. J. Hethersett, Norwich: Horizon Scientific Press;
    [Google Scholar]
  7. Lischka P., Rosorius O., Trommer E., Stamminger T. 2001; A novel transferable nuclear export signal mediates CRM1-independent nucleocytoplasmic shuttling of the human cytomegalovirus transactivator protein pUL69. EMBO J 20:7271–7283 [CrossRef]
    [Google Scholar]
  8. Lischka P., Sorg G., Kann M., Winkler M., Stamminger T. 2003; A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway. J Virol 77:3734–3748 [CrossRef]
    [Google Scholar]
  9. Lischka P., Toth Z., Thomas M., Mueller R., Stamminger T. 2006; The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA. Mol Cell Biol 26:1631–1643 [CrossRef]
    [Google Scholar]
  10. Malik P., Clements J. B. 2004; Protein kinase CK2 phosphorylation regulates the interaction of Kaposi's sarcoma-associated herpesvirus regulatory protein ORF57 with its multifunctional partner hnRNP K. Nucleic Acids Res 32:5553–5569 [CrossRef]
    [Google Scholar]
  11. Mears W. E., Rice S. A. 1996; The RGG box motif of the herpes simplex virus ICP27 protein mediates an RNA-binding activity and determines in vivo methylation. J Virol 70:7445–7453
    [Google Scholar]
  12. Mische C. C., Javanbakht H., Song B., Diaz-Griffero F., Stremlau M., Strack B., Si Z., Sodroski J. 2005; Retroviral restriction factor TRIM5alpha is a trimer. J Virol 79:14446–14450 [CrossRef]
    [Google Scholar]
  13. Sandri-Goldin R. M. 1998; ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes Dev 12:868–879 [CrossRef]
    [Google Scholar]
  14. Sandri-Goldin R. M. 2004; Viral regulation of mRNA export. J Virol 78:4389–4396 [CrossRef]
    [Google Scholar]
  15. Sciabica K. S., Dai Q. J., Sandri-Goldin R. M. 2003; ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation. EMBO J 22:1608–1619 [CrossRef]
    [Google Scholar]
  16. Soliman T. M., Silverstein S. J. 2000; Identification of an export control sequence and a requirement for the KH domains in ICP27 from herpes simplex virus type 1. J Virol 74:7600–7609 [CrossRef]
    [Google Scholar]
  17. Toth Z., Lischka P., Stamminger T. 2006; RNA-binding of the human cytomegalovirus transactivator protein UL69, mediated by arginine-rich motifs, is not required for nuclear export of unspliced RNA. Nucleic Acids Res 34:1237–1249 [CrossRef]
    [Google Scholar]
  18. Wadd S., Bryant H., Filhol O., Scott J. E., Hsieh T. Y., Everett R. D., Clements J. B. 1999; The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2. J Biol Chem 274:28991–28998 [CrossRef]
    [Google Scholar]
  19. Winkler M., Stamminger T. 1996; A specific subform of the human cytomegalovirus transactivator protein pUL69 is contained within the tegument of virus particles. J Virol 70:8984–8987
    [Google Scholar]
  20. Winkler M., aus Dem Siepen T., Stamminger T. 2000; Functional interaction between pleiotropic transactivator pUL69 of human cytomegalovirus and the human homolog of yeast chromatin regulatory protein SPT6. J Virol 74:8053–8064 [CrossRef]
    [Google Scholar]
  21. Zhi Y., Sciabica K. S., Sandri-Goldin R. M. 1999; Self-interaction of the herpes simplex virus type 1 regulatory protein ICP27. Virology 257:341–351 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82480-0
Loading
/content/journal/jgv/10.1099/vir.0.82480-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error