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 Boyle, S. M.
Right arrow Articles by Swaminathan, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boyle, S. M.
Right arrow Articles by Swaminathan, S.

 Previous Article  |  Next Article 

Journal of Virology, August 1999, p. 6872-6881, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Association with the Cellular Export Receptor CRM 1 Mediates Function and Intracellular Localization of Epstein-Barr Virus SM Protein, a Regulator of Gene Expression

Sarah M. Boyle,1 Vivian Ruvolo,1 Ashish K. Gupta,1 and Sankar Swaminathan1,2,*

Sealy Center for Oncology and Hematology and Division of Infectious Diseases, Department of Internal Medicine,1 and Department of Microbiology and Immunology,2 University of Texas Medical Branch, Galveston, Texas 77555-1048

Received 25 February 1999/Accepted 10 May 1999

Splicing and posttranscriptional processing of eukaryotic gene transcripts are linked to their nuclear export and cytoplasmic expression. Unspliced pre-mRNAs and intronless transcripts are thus inherently poorly expressed. Nevertheless, human and animal viruses encode essential genes as single open reading frames or in the intervening sequences of other genes. Many retroviruses have evolved mechanisms to facilitate nuclear export of their unspliced mRNAs. For example, the human immunodeficiency virus RNA-binding protein Rev associates with the soluble cellular export receptor CRM 1 (exportin 1), which mediates nucleocytoplasmic translocation of Rev-HIV RNA complexes through the nuclear pore. The transforming human herpesvirus Epstein-Barr virus (EBV) expresses a nuclear protein, SM, early in its lytic cycle; SM binds RNA and posttranscriptionally activates expression of certain intronless lytic EBV genes. Here we show that both the trans-activation function and cytoplasmic translocation of SM are dependent on association with CRM 1 in vivo. SM is also shown to be associated in vivo with other components of the CRM 1 export pathway, including the small GTPase Ran and the nucleoporin CAN/Nup214. SM is shown to be present in the cytoplasm, nucleoplasm, and nuclear envelope of transfected cells. Mutation of a leucine-rich region (LRR) of SM inhibited CRM 1-mediated cytoplasmic translocation and SM activity, as did leptomycin B, an inhibitor of CRM 1 complex formation. Surprisingly, however, leptomycin B treatment and mutation of the LRR both led to SM becoming more tightly attached to intranuclear structures. These findings suggest a model in which SM is not merely a soluble carrier protein for RNA but rather is bound directly to intranuclear proteins, possibly including the nuclear pore complex.

* Corresponding author. Mailing address: Sealy Center for Oncology and Hematology, MRB 9.104, University of Texas Medical Branch, Galveston, TX 77555-1048. Phone: (409) 747-1935. Fax: (409) 747-1938. E-mail: sswamina{at}utmb.edu.

Journal of Virology, August 1999, p. 6872-6881, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Han, Z., Verma, D., Hilscher, C., Dittmer, D. P., Swaminathan, S. (2009). General and Target-Specific RNA Binding Properties of Epstein-Barr Virus SM Posttranscriptional Regulatory Protein. J. Virol. 83: 11635-11644 [Abstract] [Full Text]  
  • Verma, D., Ling, C., Johannsen, E., Nagaraja, T., Swaminathan, S. (2009). Negative Autoregulation of Epstein-Barr Virus (EBV) Replicative Gene Expression by EBV SM Protein. J. Virol. 83: 8041-8050 [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]  
  • 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]  
  • 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]  
  • 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]  
  • Malik, P., Blackbourn, D. J., Clements, J. B. (2004). The Evolutionarily Conserved Kaposi's Sarcoma-associated Herpesvirus ORF57 Protein Interacts with REF Protein and Acts as an RNA Export Factor. J. Biol. Chem. 279: 33001-33011 [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]  
  • 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]  
  • 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]  
  • Donnelly, M., Elliott, G. (2001). Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14. J. Virol. 75: 2566-2574 [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]  
  • Elton, D., Simpson-Holley, M., Archer, K., Medcalf, L., Hallam, R., McCauley, J., Digard, P. (2001). Interaction of the Influenza Virus Nucleoprotein with the Cellular CRM1-Mediated Nuclear Export Pathway. J. Virol. 75: 408-419 [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]  
  • 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]  
  • 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]  


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