PMID:17267505

Citation	Xie, B, Invernizzi, CF, Richard, S and Wainberg, MA (2007) 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. J. Virol. 81:4226-34
Abstract	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.
Links	PubMed PMC1866113 Online version:10.1128/JVI.01888-06
Keywords	Arginine/metabolism; Cell Line; Chloramphenicol O-Acetyltransferase/biosynthesis; Cyclin T; Cyclins/metabolism; Gene Products, tat/metabolism; Gene Silencing; Genes, Reporter; HIV-1/growth & development; HIV-1/immunology; Humans; Luciferases/biosynthesis; Luciferases/genetics; Methylation; Nuclear Proteins/metabolism; Protein Binding; Protein-Arginine N-Methyltransferases/metabolism; RNA, Viral/metabolism; Transcription, Genetic; Transcriptional Activation; Virus Replication; tat Gene Products, Human Immunodeficiency Virus
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ANM6		GO:0016274: protein-arginine N-methyltransferase activity	ECO:0000314:		F		Figure 2	complete CACAO 3529

References

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