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Journal of Virology, January 2008, p. 775-784, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.02107-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Conserved Motif in Region V of the Large Polymerase Proteins of Nonsegmented Negative-Sense RNA Viruses That Is Essential for mRNA Capping{triangledown}

Jianrong Li,{dagger} Amal Rahmeh,{dagger} Marco Morelli, and Sean P. J. Whelan*

Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, Massachusetts 02115

Received 22 September 2007/ Accepted 26 October 2007

Nonsegmented negative-sense (NNS) RNA viruses cap their mRNA by an unconventional mechanism. Specifically, 5' monophosphate mRNA is transferred to GDP derived from GTP through a reaction that involves a covalent intermediate between the large polymerase protein L and mRNA. This polyribonucleotidyltransferase activity contrasts with all other capping reactions, which are catalyzed by an RNA triphosphatase and guanylyltransferase. In these reactions, a 5' diphosphate mRNA is capped by transfer of GMP via a covalent enzyme-GMP intermediate. RNA guanylyltransferases typically have a KxDG motif in which the lysine forms this covalent intermediate. Consistent with the distinct mechanism of capping employed by NNS RNA viruses, such a motif is absent from L. To determine the residues of L protein required for capping, we reconstituted the capping reaction of the prototype NNS RNA virus, vesicular stomatitis virus, from highly purified components. Using a panel of L proteins with single-amino-acid substitutions to residues universally conserved among NNS RNA virus L proteins, we define a new motif, GxxT[n]HR, present within conserved region V of L protein that is essential for this unconventional mechanism of mRNA cap formation.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-1923. Fax: (617) 738-7664. E-mail: swhelan{at}hms.harvard.edu

{triangledown} Published ahead of print on 14 November 2007.

{dagger} J.L. and A.R. made equal contributions to this article.

Journal of Virology, January 2008, p. 775-784, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.02107-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ruedas, J. B., Perrault, J. (2009). Insertion of Enhanced Green Fluorescent Protein in a Hinge Region of Vesicular Stomatitis Virus L Polymerase Protein Creates a Temperature-Sensitive Virus That Displays No Virion-Associated Polymerase Activity In Vitro. J. Virol. 83: 12241-12252 [Abstract] [Full Text]  
  • Rahmeh, A. A., Li, J., Kranzusch, P. J., Whelan, S. P. J. (2009). Ribose 2'-O Methylation of the Vesicular Stomatitis Virus mRNA Cap Precedes and Facilitates Subsequent Guanine-N-7 Methylation by the Large Polymerase Protein. J. Virol. 83: 11043-11050 [Abstract] [Full Text]  
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