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Journal of Virology, July 2008, p. 7180-7188, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.00344-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus SM Protein Functions as an Alternative Splicing Factor {triangledown}

Dinesh Verma1 and Sankar Swaminathan1,2*

University of Florida Shands Cancer Center,1 Division of Infectious Diseases, Department of Medicine and Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 326102

Received 17 February 2008/ Accepted 1 May 2008

Alternative splicing of RNA increases the coding potential of the genome and allows for additional regulatory control over gene expression. The full extent of alternative splicing remains to be defined but is likely to significantly expand the size of the human transcriptome. There are several examples of mammalian viruses regulating viral splicing or inhibiting cellular splicing in order to facilitate viral replication. Here, we describe a viral protein that induces alternative splicing of a cellular RNA transcript. Epstein-Barr virus (EBV) SM protein is a viral protein essential for replication that enhances EBV gene expression by enhancing RNA stability and export. SM also increases cellular STAT1 expression, a central mediator of interferon signal transduction, but disproportionately increases the abundance of the STAT1β splicing isoform, which can act as a dominant-negative suppressor of STAT1{alpha}. SM induces splicing of STAT1 at a novel 5' splice site, resulting in a STAT1 mRNA incapable of producing STAT1{alpha}. SM-induced alternative splicing is dependent on the presence of an RNA sequence to which SM binds directly and which can confer SM-dependent splicing on heterologous RNA. The cellular splicing factor ASF/SF2 also binds to this region and inhibits SM-RNA binding and SM-induced alternative splicing. These results suggest that viruses may regulate cellular gene expression at the level of alternative mRNA splicing in order to facilitate virus replication or persistence in vivo.

* Corresponding author. Mailing address: University of Florida Shands Cancer Center, University of Florida, 1376 Mowry Road, Gainesville, FL 32610-3633. Phone: (352) 273-8206. Fax: (352) 273-8299. E-mail: sswamina{at}ufl.edu

{triangledown} Published ahead of print on 7 May 2008.

Journal of Virology, July 2008, p. 7180-7188, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.00344-08
Copyright © 2008, 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]  
  • Nojima, T., Oshiro-Ideue, T., Nakanoya, H., Kawamura, H., Morimoto, T., Kawaguchi, Y., Kataoka, N., Hagiwara, M. (2009). Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing. Nucleic Acids Res 37: 6515-6527 [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]  
  • 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]  


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