This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xie, B.
Right arrow Articles by Wainberg, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xie, B.
Right arrow Articles by Wainberg, M. A.

 Previous Article  |  Next Article 

Journal of Virology, April 2007, p. 4226-4234, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01888-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Arginine Methylation of the Human Immunodeficiency Virus Type 1 Tat Protein by PRMT6 Negatively Affects Tat Interactions with both Cyclin T1 and the Tat Transactivation Region{triangledown}

Baode Xie,1,{dagger} Cédric F. Invernizzi,1,4,{dagger} Stéphane Richard,2,3,4,5 and Mark A. Wainberg1,4*

McGill University AIDS Centre,1 Terry Fox Molecular Oncology Group,2 Bloomfield Centre for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital,3 Departments of Medicine,4 Oncology, McGill University, Montréal, Québec, Canada5

Received 30 August 2006/ Accepted 24 January 2007

Arginine methylation has been shown to regulate signal transduction, protein subcellular localization, gene transcription, and protein-protein interactions that ultimately alter gene expression. Although the role of cellular protein arginine methyltransferases (PRMT) in viral gene expression is largely unknown, we recently showed that the Tat protein of human immunodeficiency virus type 1 (HIV-1) is a substrate for one such enzyme, termed PRMT6. However, the mechanism by which arginine methylation impairs the transactivation potential of Tat and the sites of arginine methylation within Tat remain obscure. We now show that Tat is a specific in vitro and in vivo substrate of PRMT6 which targets the Tat R52 and R53 residues for arginine methylation. Such Tat methylation led to decreased interaction with the Tat transactivation region (TAR) of viral RNA. Furthermore, arginine methylation of Tat negatively affected Tat-TAR-cyclin T1 ternary complex formation and diminished cyclin T1-dependent Tat transcriptional activation. Overexpression of wild-type PRMT6, but not a methylase-inactive PRMT6 mutant, reduced levels of Tat transactivation of HIV-1 long terminal repeat chloramphenicol acetyltransferase and luciferase reporter plasmids in a dose-dependent manner. In cell-based assays, knockdown of PRMT6 resulted in increased HIV-1 production and faster viral replication. Thus, PRMT6 can compromise Tat transcriptional activation and may represent a form of innate cellular immunity in regard to HIV-1 replication. Finding a way of inhibiting or stimulating PRMT6 activity might help to drive quiescently infected cells out of latency or combat HIV-1 replication, respectively.

* Corresponding author. Mailing address: McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, 3755 Côte-Ste-Catherine Rd., Montréal, Québec H3T 1E2, Canada. Phone: (514) 340-8260. Fax: (514) 340-8295. E-mail: mark.wainberg{at}mcgill.ca

{triangledown} Published ahead of print on 31 January 2007.

{dagger} B.X. and C.F.I. contributed equally to this work.

Journal of Virology, April 2007, p. 4226-4234, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01888-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sivakumaran, H., van der Horst, A., Fulcher, A. J., Apolloni, A., Lin, M.-H., Jans, D. A., Harrich, D. (2009). Arginine Methylation Increases the Stability of Human Immunodeficiency Virus Type 1 Tat. J. Virol. 83: 11694-11703 [Abstract] [Full Text]  
  • Mitchell, T. R. H., Glenfield, K., Jeyanthan, K., Zhu, X.-D. (2009). Arginine Methylation Regulates Telomere Length and Stability. Mol. Cell. Biol. 29: 4918-4934 [Abstract] [Full Text]  
  • Michaud-Levesque, J., Richard, S. (2009). Thrombospondin-1 Is a Transcriptional Repression Target of PRMT6. J. Biol. Chem. 284: 21338-21346 [Abstract] [Full Text]  
  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  
  • Cheng, C.-W., Hsiao, Y.-Y., Wu, H.-C., Chuang, C.-M., Chen, J.-S., Tsai, C.-H., Hsu, Y.-H., Wu, Y.-C., Lee, C.-C., Meng, M. (2009). Suppression of Bamboo Mosaic Virus Accumulation by a Putative Methyltransferase in Nicotiana benthamiana. J. Virol. 83: 5796-5805 [Abstract] [Full Text]  
  • Souki, S. K., Gershon, P. D., Sandri-Goldin, R. M. (2009). Arginine Methylation of the ICP27 RGG Box Regulates ICP27 Export and Is Required for Efficient Herpes Simplex Virus 1 Replication. J. Virol. 83: 5309-5320 [Abstract] [Full Text]  
  • Kim, M. J., Huh, S. U., Ham, B.-K., Paek, K.-H. (2008). A Novel Methyltransferase Methylates Cucumber Mosaic Virus 1a Protein and Promotes Systemic Spread. J. Virol. 82: 4823-4833 [Abstract] [Full Text]  
  • Lakowski, T. M., Frankel, A. (2008). A Kinetic Study of Human Protein Arginine N-Methyltransferase 6 Reveals a Distributive Mechanism. J. Biol. Chem. 283: 10015-10025 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»