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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.


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