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Journal of Virology, December 2008, p. 12280-12290, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01225-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

S-Adenosyl Homocysteine-Induced Hyperpolyadenylation of Vesicular Stomatitis Virus mRNA Requires the Methyltransferase Activity of L Protein{triangledown}

Summer E. Galloway1 and Gail W. Wertz1,2*

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama,1 Department of Pathology, University of Virginia, Charlottesville, Virginia2

Received 12 June 2008/ Accepted 11 September 2008

There are many unique aspects of vesicular stomatitis virus (VSV) transcription. In addition to its unusual mRNA capping and methyltransferase mechanisms, the addition of S-adenosyl homocysteine (SAH), which is the by-product and competitive inhibitor of S-adenosyl methionine (SAM)-mediated methyltransferase reactions, leads to synthesis of poly(A) tails on the 3' end of VSV mRNAs that are 10- or 20-fold longer than normal. The mechanism by which this occurs is not understood, since it has been shown that productive transcription is not dependent on 5' cap methylation and full-length VSV mRNAs can be synthesized in the absence of SAM. To investigate this unusual phenotype, we assayed the effects of SAH on transcription using a panel of recombinant viruses that contained mutations in domain VI of the VSV L protein. The L proteins we investigated displayed a range of 5' cap methyltransferase activities. In the present study, we show that the ability of the VSV L protein to catalyze methyl transfer correlates with its sensitivity to SAH with respect to polyadenylation, thereby indicating an intriguing connection between 5' and 3' end mRNA modifications. We also identified an L protein mutant that hyperpolyadenylates mRNA irrespective of the presence or absence of exogenous SAH. Further, the data presented here show that the wild-type L protein hyperpolyadenylates a percentage of VSV mRNAs in infected cells as well as in vitro.


* Corresponding author. Mailing address: Department of Pathology, University of Virginia, MR5 Building, P.O. Box 800904, Charlottesville, VA 22908-0904. Phone: (434) 982-6039. Fax: (434) 982-2151. E-mail: gww4f{at}virginia.edu

{triangledown} Published ahead of print on 1 October 2008.


Journal of Virology, December 2008, p. 12280-12290, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01225-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Li, J., Rahmeh, A., Brusic, V., Whelan, S. P. J. (2009). Opposing Effects of Inhibiting Cap Addition and Cap Methylation on Polyadenylation during Vesicular Stomatitis Virus mRNA Synthesis. J. Virol. 83: 1930-1940 [Abstract] [Full Text]