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PMID:15596808
| Citation |
Boulanger, MC, Liang, C, Russell, RS, Lin, R, Bedford, MT, Wainberg, MA and Richard, S (2005) Methylation of Tat by PRMT6 regulates human immunodeficiency virus type 1 gene expression. J. Virol. 79:124-31 |
|---|---|
| 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. |
| Links |
PubMed PMC538702 Online version:10.1128/JVI.79.1.124-131.2005 |
| Keywords |
Amino Acid Sequence; Gene Expression Regulation, Viral; Gene Products, tat/chemistry; Gene Products, tat/genetics; Gene Products, tat/metabolism; HIV Core Protein p24/genetics; HIV Core Protein p24/metabolism; HIV-1/genetics; HIV-1/metabolism; HIV-1/physiology; HeLa Cells; Humans; Methylation; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein-Arginine N-Methyltransferases/genetics; Protein-Arginine N-Methyltransferases/metabolism; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Transcription, Genetic; Transfection; tat Gene Products, Human Immunodeficiency Virus |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0016274: protein-arginine N-methyltransferase activity |
ECO:0000314: |
F |
Figure 3 |
complete | ||||
See also
References
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