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Journal of Virology, January 2005, p. 124-131, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.124-131.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Methylation of Tat by PRMT6 Regulates Human Immunodeficiency Virus Type 1 Gene Expression

Marie-Chloé Boulanger,1,2 Chen Liang,3 Rodney S. Russell,3,4 Rongtuan Lin,1,5 Mark T. Bedford,6 Mark A. Wainberg,3,4* and Stéphane Richard1,2,5,7*

Terry Fox Molecular Oncology Group,1 Bloomfield Center for Research on Aging,2 McGill University AIDS Center, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital,3 Departments of Microbiology,4 Medicine,5 Oncology, McGill University, Montréal, Québec, Canada,7 M.D. Anderson Cancer Center, Department of Carcinogenesis, University of Texas, Smithville, Texas6

Received 13 May 2004/ Accepted 27 August 2004

The human immunodeficiency virus (HIV) transactivator protein, Tat, stimulates transcription from the viral long terminal repeats via an arginine-rich transactivating domain. Since arginines are often known to be methylated, we investigated whether HIV type 1 (HIV-1) Tat was a substrate for known protein arginine methyltransferases (PRMTs). Here we identify Tat as a substrate for the arginine methyltransferase, PRMT6. Tat is specifically associated with and methylated by PRMT6 within cells. Overexpression of wild-type PRMT6, but not a methylase-inactive PRMT6 mutant, decreased Tat transactivation of an HIV-1 long terminal repeat luciferase reporter plasmid in a dose-dependent manner. Knocking down PRMT6 consistently increased HIV-1 production in HEK293T cells and also led to increased viral infectiousness as shown in multinuclear activation of a galactosidase indicator assays. Our study demonstrates that arginine methylation of Tat negatively regulates its transactivation activity and that PRMT6 acts as a restriction factor for HIV replication.


* Corresponding author. Mailing address: Lady Davis Institute, 3755 Côte Ste-Catherine Rd., Montréal, Québec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-8295. E-mail for Mark A. Wainberg: mark.wainberg{at}mcgill.ca. E-mail for Stéphane Richard: stephane.richard{at}mcgill.ca.


Journal of Virology, January 2005, p. 124-131, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.124-131.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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