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Journal of Virology, November 2009, p. 11635-11644, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01483-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

General and Target-Specific RNA Binding Properties of Epstein-Barr Virus SM Posttranscriptional Regulatory Protein{triangledown}

Zhao Han,1 Dinesh Verma,1 Chelsey Hilscher,2 Dirk P. Dittmer,2 and Sankar Swaminathan1*

Division of Infectious Diseases, Department of Medicine, and University of Florida Shands Cancer Center, University of Florida, Gainesville, Florida,1 Department of Microbiology and Immunology, Center for AIDS Research, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina2

Received 16 July 2009/ Accepted 24 August 2009

Epstein-Barr virus (EBV) SM protein is an essential nuclear shuttling protein expressed by EBV early during the lytic phase of replication. SM acts to increase EBV lytic gene expression by binding EBV mRNAs and enhancing accumulation of the majority of EBV lytic cycle mRNAs. SM increases target mRNA stability and nuclear export, in addition to modulating RNA splicing. SM and its homologs in other herpesvirus have been hypothesized to function in part by binding viral RNAs and recruiting cellular export factors. Although activation of gene expression by SM is gene specific, it is unknown whether SM binds to mRNA in a specific manner or whether its RNA binding is target independent. SM-mRNA complexes were isolated from EBV-infected B-lymphocyte cell lines induced to permit lytic EBV replication, and a quantitative measurement of mRNAs corresponding to all known EBV open reading frames was performed by real-time quantitative reverse transcription-PCR. The results showed that although SM has broad RNA binding properties, there is a clear hierarchy of affinities among EBV mRNAs with respect to SM complex formation. In vitro binding assays with two of the most highly SM-associated transcripts suggested that SM binds preferentially to specific sequences or structures present in noncoding regions of some EBV mRNAs. Furthermore, the presence of these sequences conferred responsiveness to SM. These data are consistent with a mechanism of action similar to that of hnRNPs, which exert sequence-specific effects on gene expression despite having multiple degenerate consensus binding sites common to a large number of RNAs.

* Corresponding author. Mailing address: 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 2 September 2009.

Journal of Virology, November 2009, p. 11635-11644, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01483-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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