This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Semmes, O. J.
Right arrow Articles by Hayward, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Semmes, O. J.
Right arrow Articles by Hayward, S. D.

 Previous Article  |  Next Article 

Journal of Virology, December 1998, p. 9526-9534, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mta Has Properties of an RNA Export Protein and Increases Cytoplasmic Accumulation of Epstein-Barr Virus Replication Gene mRNA

O. John Semmes,1,2 Lin Chen,1 Robert T. Sarisky,1 Zhigang Gao,1 Ling Zhong,1 and S. Diane Hayward1,3,*

Molecular Virology Laboratories, Department of Pharmacology and Molecular Sciences,1 and Department of Oncology,3 Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and Department of Microbiology, University of Virginia Medical School, Charlottesville, Virginia 229082

Received 7 July 1998/Accepted 9 September 1998

The Epstein-Barr virus (EBV) Zta and Mta regulatory proteins were previously found to be required for efficient replication of oriLyt in cotransfection-replication assays, but the contribution of Mta to the replication process was unknown. We now demonstrate that Mta regulates replication gene expression. Using the polymerase processivity factor BMRF1 as an example, we found that in transfected cells, total BMRF1 mRNA levels were unaffected by Mta but that the amounts of cytoplasmic BMRF1 RNA and protein were greatly increased in the presence of Mta. Mta also increased cytoplasmic accumulation of the BALF2, BALF5, BSLF1, and BBLF4 replication gene mRNAs but did not affect cytoplasmic levels of BBLF2/3 mRNA. Thus, five of the six core replication genes require Mta for efficient accumulation of cytoplasmic RNA. The contribution of Mta to posttranscriptional RNA processing was examined. Examination of Mta localization in transfected cells by indirect immunofluorescence revealed that Mta colocalized with the splicing factor SC35. We also found that Mta has RNA binding activity. Glutathione S-transferase-Mta bound to BMRF1 and BMLF1 transcripts but not to a control cellular gene RNA. Mta contains a consensus leucine-rich nuclear export signal. Such signal sequences are characteristic of proteins that undergo nuclear export. Examination of Mta localization in a heterokaryon assay provided evidence that Mta shuttles between the nucleus and the cytoplasm. Our experiments indicate that Mta functions in RNA processing and transport and mediates cytoplasmic accumulation of a number of EBV early mRNAs.

* Corresponding author. Mailing address: Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205-2185. Phone: (410) 955-2548. Fax: (410) 955-8685. E-mail: diane_hayward{at}qmail.bs.jhu.edu.

Journal of Virology, December 1998, p. 9526-9534, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zhu, J., Liao, G., Shan, L., Zhang, J., Chen, M.-R., Hayward, G. S., Hayward, S. D., Desai, P., Zhu, H. (2009). Protein Array Identification of Substrates of the Epstein-Barr Virus Protein Kinase BGLF4. J. Virol. 83: 5219-5231 [Abstract] [Full Text]  
  • Colgan, K. J., Boyne, J. R., Whitehouse, A. (2009). Identification of a response element in a herpesvirus saimiri mRNA recognized by the ORF57 protein. J. Gen. Virol. 90: 596-601 [Abstract] [Full Text]  
  • Verma, D., Swaminathan, S. (2008). Epstein-Barr Virus SM Protein Functions as an Alternative Splicing Factor. J. Virol. 82: 7180-7188 [Abstract] [Full Text]  
  • Medina-Palazon, C., Gruffat, H., Mure, F., Filhol, O., Vingtdeux-Didier, V., Drobecq, H., Cochet, C., Sergeant, N., Sergeant, A., Manet, E. (2007). Protein Kinase CK2 Phosphorylation of EB2 Regulates Its Function in the Production of Epstein-Barr Virus Infectious Viral Particles. J. Virol. 81: 11850-11860 [Abstract] [Full Text]  
  • Han, Z., Marendy, E., Wang, Y.-D., Yuan, J., Sample, J. T., Swaminathan, S. (2007). Multiple Roles of Epstein-Barr Virus SM Protein in Lytic Replication. J. Virol. 81: 4058-4069 [Abstract] [Full Text]  
  • Han, Z., Swaminathan, S. (2006). Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene ORF57 Is Essential for Infectious Virion Production.. J. Virol. 80: 5251-5260 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Hiriart, E., Gruffat, H., Buisson, M., Mikaelian, I., Keppler, S., Meresse, P., Mercher, T., Bernard, O. A., Sergeant, A., Manet, E. (2005). Interaction of the Epstein-Barr Virus mRNA Export Factor EB2 with Human Spen Proteins SHARP, OTT1, and a Novel Member of the Family, OTT3, Links Spen Proteins with Splicing Regulation and mRNA Export. J. Biol. Chem. 280: 36935-36945 [Abstract] [Full Text]  
  • Xu, Y., AuCoin, D. P., Huete, A. R., Cei, S. A., Hanson, L. J., Pari, G. S. (2005). A Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50 Deletion Mutant Is Defective for Reactivation of Latent Virus and DNA Replication. J. Virol. 79: 3479-3487 [Abstract] [Full Text]  
  • Liao, G., Huang, J., Fixman, E. D., Hayward, S. D. (2005). The Epstein-Barr Virus Replication Protein BBLF2/3 Provides an Origin-Tethering Function through Interaction with the Zinc Finger DNA Binding Protein ZBRK1 and the KAP-1 Corepressor. J. Virol. 79: 245-256 [Abstract] [Full Text]  
  • Nicewonger, J., Suck, G., Bloch, D., Swaminathan, S. (2004). Epstein-Barr Virus (EBV) SM Protein Induces and Recruits Cellular Sp110b To Stabilize mRNAs and Enhance EBV Lytic Gene Expression. J. Virol. 78: 9412-9422 [Abstract] [Full Text]  
  • Sandri-Goldin, R. M. (2004). Viral Regulation of mRNA Export. J. Virol. 78: 4389-4396 [Full Text]  
  • Ruvolo, V., Sun, L., Howard, K., Sung, S., Delecluse, H.-J., Hammerschmidt, W., Swaminathan, S. (2004). Functional Analysis of Epstein-Barr Virus SM Protein: Identification of Amino Acids Essential for Structure, Transactivation, Splicing Inhibition, and Virion Production. J. Virol. 78: 340-352 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Ruvolo, V., Navarro, L., Sample, C. E., David, M., Sung, S., Swaminathan, S. (2003). The Epstein-Barr Virus SM Protein Induces STAT1 and Interferon-Stimulated Gene Expression. J. Virol. 77: 3690-3701 [Abstract] [Full Text]  
  • Hiriart, E., Farjot, G., Gruffat, H., Nguyen, M. V. C., Sergeant, A., Manet, E. (2003). A Novel Nuclear Export Signal and a REF Interaction Domain Both Promote mRNA Export by the Epstein-Barr Virus EB2 Protein. J. Biol. Chem. 278: 335-342 [Abstract] [Full Text]  
  • Poppers, J., Mulvey, M., Perez, C., Khoo, D., Mohr, I. (2002). Identification of a Lytic-Cycle Epstein-Barr Virus Gene Product That Can Regulate PKR Activation. J. Virol. 77: 228-236 [Abstract] [Full Text]  
  • Gruffat, H., Batisse, J., Pich, D., Neuhierl, B., Manet, E., Hammerschmidt, W., Sergeant, A. (2002). Epstein-Barr Virus mRNA Export Factor EB2 Is Essential for Production of Infectious Virus. J. Virol. 76: 9635-9644 [Abstract] [Full Text]  
  • Boyer, J. L., Swaminathan, S., Silverstein, S. J. (2002). The Epstein-Barr Virus SM Protein Is Functionally Similar to ICP27 from Herpes Simplex Virus in Viral Infections. J. Virol. 76: 9420-9433 [Abstract] [Full Text]  
  • Popa, I., Harris, M. E., Donello, J. E., Hope, T. J. (2002). CRM1-Dependent Function of a cis-Acting RNA Export Element. Mol. Cell. Biol. 22: 2057-2067 [Abstract] [Full Text]  
  • Ruvolo, V., Gupta, A. K., Swaminathan, S. (2001). Epstein-Barr Virus SM Protein Interacts with mRNA In Vivo and Mediates a Gene-Specific Increase in Cytoplasmic mRNA. J. Virol. 75: 6033-6041 [Abstract] [Full Text]  
  • Wu, F. Y., Ahn, J.-H., Alcendor, D. J., Jang, W.-J., Xiao, J., Hayward, S. D., Hayward, G. S. (2001). Origin-Independent Assembly of Kaposi's Sarcoma-Associated Herpesvirus DNA Replication Compartments in Transient Cotransfection Assays and Association with the ORF-K8 Protein and Cellular PML. J. Virol. 75: 1487-1506 [Abstract] [Full Text]  
  • Murata, T., Goshima, F., Koshizuka, T., Takakuwa, H., Nishiyama, Y. (2001). A Single Amino Acid Substitution in the ICP27 Protein of Herpes Simplex Virus Type 1 Is Responsible for Its Resistance to Leptomycin B. J. Virol. 75: 1039-1043 [Abstract] [Full Text]  
  • Peng, R., Tan, J., Ling, P. D. (2000). Conserved Regions in the Epstein-Barr Virus Leader Protein Define Distinct Domains Required for Nuclear Localization and Transcriptional Cooperation with EBNA2. J. Virol. 74: 9953-9963 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Farjot, G., Buisson, M., Duc Dodon, M., Gazzolo, L., Sergeant, A., Mikaelian, I. (2000). Epstein-Barr Virus EB2 Protein Exports Unspliced RNA via a Crm-1-Independent Pathway. J. Virol. 74: 6068-6076 [Abstract] [Full Text]  
  • Kirshner, J. R., Lukac, D. M., Chang, J., Ganem, D. (2000). Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 57 Encodes a Posttranscriptional Regulator with Multiple Distinct Activities. J. Virol. 74: 3586-3597 [Abstract] [Full Text]  
  • Soliman, T. M., Silverstein, S. J. (2000). Herpesvirus mRNAs Are Sorted for Export via Crm1-Dependent and -Independent Pathways. J. Virol. 74: 2814-2825 [Abstract] [Full Text]  
  • Burton, M., Upadhyaya, C. D., Maier, B., Hope, T. J., Semmes, O. J. (2000). Human T-Cell Leukemia Virus Type 1 Tax Shuttles between Functionally Discrete Subcellular Targets. J. Virol. 74: 2351-2364 [Abstract] [Full Text]  
  • Gupta, A. K., Ruvolo, V., Patterson, C., Swaminathan, S. (2000). The Human Herpesvirus 8 Homolog of Epstein-Barr Virus SM Protein (KS-SM) Is a Posttranscriptional Activator of Gene Expression. J. Virol. 74: 1038-1044 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Boyle, S. M., Ruvolo, V., Gupta, A. K., Swaminathan, S. (1999). Association with the Cellular Export Receptor CRM 1 Mediates Function and Intracellular Localization of Epstein-Barr Virus SM Protein, a Regulator of Gene Expression. J. Virol. 73: 6872-6881 [Abstract] [Full Text]  
  • Buisson, M., Hans, F., Kusters, I., Duran, N., Sergeant, A. (1999). The C-Terminal Region but Not the Arg-X-Pro Repeat of Epstein-Barr Virus Protein EB2 Is Required for Its Effect on RNA Splicing and Transport. J. Virol. 73: 4090-4100 [Abstract] [Full Text]  
  • Cooper, M, Goodwin, D., Hall, K., Stevenson, A., Meredith, D., Markham, A., 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 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»