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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2004 Dec 15

PMID 15596808

Citations 99

Authors

Marie-Chloe Boulanger

Chen Liang

Rodney S Russell

Rongtuan Lin

Mark T Bedford

Mark A Wainberg

Stephane Richard

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex.

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Protein arginine methylation in viral infection and antiviral immunity.

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Protein arginine methyltransferase 6 is a novel substrate of protein arginine methyltransferase 1.

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Effectors and effects of arginine methylation.

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