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Journal of Virology, October 2008, p. 9823-9828, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01144-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Evolutionarily Conserved Function of a Viral MicroRNA {triangledown}

G. J. Seo,1 L. H. L. Fink,1 B. O'Hara,2 W. J. Atwood,2 and C. S. Sullivan1*

Molecular Genetics and Microbiology, The University of Texas at Austin, 1 University Station A5000, Austin, Texas 78712-0162,1 Brown University, Providence, Rhode Island 029122

Received 2 June 2008/ Accepted 3 August 2008

MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to autoregulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function (the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.

* Corresponding author. Mailing address: Molecular Genetics and Microbiology, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712-0162. Phone: (512) 471-5391. Fax: (512) 471-7088. E-mail: Chris_sullivan{at}mail.utexas.edu

{triangledown} Published ahead of print on 6 August 2008.

Journal of Virology, October 2008, p. 9823-9828, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01144-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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