1887

Abstract

The herpesvirus saimiri (HVS) ORF57 protein binds viral RNA, enabling the efficient nuclear export of intronless viral mRNAs. However, it is not known how ORF57 recognizes these viral mRNAs. In this study, a systematic evolution of ligands by exponential enrichment (SELEX) approach was used to select RNA sequences that are preferentially bound by the ORF57 protein. Results identified a recurring motif, GAAGRG, within the majority of selected RNAs, which is also present in many late HVS mRNAs. RNA immunopreciptations demonstrated that disruption of this motif within a viral intronless RNA ablates ORF57 binding. These data suggest that the GAAGRG motif may be required within a HVS intronless mRNA for recognition by the ORF57 protein.

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2009-03-01
2019-11-16
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References

  1. Bello, L. J., Davison, A. J., Glenn, M. A., Whitehouse, A., Rethmeier, N., Schulz, T. F. & Barklie Clements, J. ( 1999; ). The human herpesvirus-8 ORF 57 gene and its properties. J Gen Virol 80, 3207–3215.
    [Google Scholar]
  2. Boyne, J. R. & Whitehouse, A. ( 2006a; ). γ-2 herpes virus post-transcriptional gene regulation. Clin Microbiol Infect 12, 110–117.[CrossRef]
    [Google Scholar]
  3. Boyne, J. R. & Whitehouse, A. ( 2006b; ). Nucleolar trafficking is essential for nuclear export of intronless herpesvirus mRNA. Proc Natl Acad Sci U S A 103, 15190–15195.[CrossRef]
    [Google Scholar]
  4. Boyne, J. R., Colgan, K. J. & Whitehouse, A. ( 2008a; ). Herpesvirus saimiri ORF57: a post-transcriptional regulatory protein. Front Biosci 13, 2928–2938.[CrossRef]
    [Google Scholar]
  5. Boyne, J. R., Colgan, K. J. & Whitehouse, A. ( 2008b; ). Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog 4, e1000194 [CrossRef]
    [Google Scholar]
  6. Cooper, M., Goodwin, D. J., Hall, K. T., Stevenson, A. J., Meredith, D. M., Markham, A. F. & Whitehouse, A. ( 1999; ). The gene product encoded by ORF 57 of herpesvirus saimiri regulates the redistribution of the splicing factor SC-35. J Gen Virol 80, 1311–1316.
    [Google Scholar]
  7. Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T. & Darnell, R. B. ( 2001; ). Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107, 489–499.[CrossRef]
    [Google Scholar]
  8. Goodwin, D. J. & Whitehouse, A. ( 2001; ). A γ-2 herpesvirus nucleocytoplasmic shuttle protein interacts with importin α1 and α5. J Biol Chem 276, 19905–19912.[CrossRef]
    [Google Scholar]
  9. Goodwin, D. J., Hall, K. T., Stevenson, A. J., Markham, A. F. & Whitehouse, A. ( 1999; ). The open reading frame 57 gene product of herpesvirus saimiri shuttles between the nucleus and cytoplasm and is involved in viral RNA nuclear export. J Virol 73, 10519–10524.
    [Google Scholar]
  10. Goodwin, D. J., Hall, K. T., Giles, M. S., Calderwood, M. A., Markham, A. F. & Whitehouse, A. ( 2000; ). The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that are required for transactivation and transrepression. J Gen Virol 81, 2253–2265.
    [Google Scholar]
  11. 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]
  12. Joyce, G. F. ( 1994; ). In vitro evolution of nucleic acids. Curr Opin Struct Biol 4, 331–336.[CrossRef]
    [Google Scholar]
  13. Lerga, A., Hallier, M., Delva, L., Orvain, C., Gallais, I., Marie, J. & Moreau-Gachelin, F. ( 2001; ). Identification of an RNA binding specificity for the potential splicing factor TLS. J Biol Chem 276, 6807–6816.[CrossRef]
    [Google Scholar]
  14. Majerciak, V., Yamanegi, K., Allemand, E., Kruhlak, M., Krainer, A. R. & Zheng, Z. M. ( 2008; ). Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing. J Virol 82, 2792–2801.[CrossRef]
    [Google Scholar]
  15. Perera, L. P., Kaushal, S., Kinchington, P. R., Mosca, J. D., Hayward, G. S. & Straus, S. E. ( 1994; ). Varicella-zoster virus open reading frame 4 encodes a transcriptional activator that is functionally distinct from that of herpes simplex virus homology ICP27. J Virol 68, 2468–2477.
    [Google Scholar]
  16. Sacks, W. R., Greene, C. C., Aschman, D. P. & Schaffer, P. A. ( 1985; ). Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol 55, 796–805.
    [Google Scholar]
  17. Sandri-Goldin, R. M. ( 2008; ). The many roles of the regulatory protein ICP27 during herpes simplex virus infection. Front Biosci 13, 5241–5256.
    [Google Scholar]
  18. Schaeffer, C., Bardoni, B., Mandel, J. L., Ehresmann, B., Ehresmann, C. & Moine, H. ( 2001; ). The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J 20, 4803–4813.[CrossRef]
    [Google Scholar]
  19. Semmes, O. J., Chen, L., Sarisky, R. T., Gao, Z., Zhong, L. & Hayward, S. D. ( 1998; ). Mta has properties of an RNA export protein and increases cytoplasmic accumulation of Epstein-Barr virus replication gene mRNA. J Virol 72, 9526–9534.
    [Google Scholar]
  20. Sokolowski, M., Scott, J. E., Heaney, R. P., Patel, A. H. & Clements, J. B. ( 2003; ). Identification of herpes simplex virus RNAs that interact specifically with regulatory protein ICP27 in vivo. J Biol Chem 278, 33540–33549.[CrossRef]
    [Google Scholar]
  21. Stoltenburg, R., Reinemann, C. & Strehlitz, B. ( 2007; ). SELEX – a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng 24, 381–403.[CrossRef]
    [Google Scholar]
  22. Verma, D. & Swaminathan, S. ( 2008; ). Epstein-Barr virus SM protein functions as an alternative splicing factor. J Virol 82, 7180–7188.[CrossRef]
    [Google Scholar]
  23. Whitehouse, A., Cooper, M. & Meredith, D. M. ( 1998; ). The immediate-early gene product encoded by open reading frame 57 of herpesvirus saimiri modulates gene expression at a posttranscriptional level. J Virol 72, 857–861.
    [Google Scholar]
  24. Williams, B. J., Boyne, J. R., Goodwin, D. J., Roaden, L., Hautbergue, G. M., Wilson, S. A. & Whitehouse, A. ( 2005; ). The prototype γ-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway. Biochem J 387, 295–308.[CrossRef]
    [Google Scholar]
  25. Winkler, M., Rice, S. A. & Stamminger, T. ( 1994; ). UL69 of human cytomegalovirus, an open reading frame with homology to ICP27 of herpes simplex virus, encodes a transactivator of gene expression. J Virol 68, 3943–3954.
    [Google Scholar]
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