Disease relevance of PRMT6

• In cell-based assays, knockdown of PRMT6 resulted in increased HIV-1 production and faster viral replication [1].
• 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 [1].

High impact information on PRMT6

• Two residues, R83 and R152, were identified in Pol beta as the sites of methylation by PRMT6 [2].
• Methylation of Pol beta by PRMT6 strongly stimulated DNA polymerase activity by enhancing DNA binding and processivity, while single nucleotide insertion and dRP-lyase activity were not affected [2].
• The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6 [3].
• In addition, PRMT6 displays automethylation activity; it is the first PRMT to do so [4].
• A comparison of substrate specificity reveals that PRMT6 is functionally distinct from two previously characterized type I enzymes, PRMT1 and PRMT4 [4].

Chemical compound and disease context of PRMT6

• 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 [1].

Associations of PRMT6 with chemical compounds

• Upon retinoic acid-induced transcriptional activation of HoxA2 in a cell model of neuronal differentiation, PRMT6 recruitment and H3 R2 methylation are diminished and H3 K4 trimethylation increases at the gene [5].
• We speculate that the increased catalytic efficiency of PRMT6 for methylated substrates combined with lower K(m) values for native protein methyl acceptors may obscure this distributive mechanism to produce an apparently processive mechanism [6].

Biological context of PRMT6

• 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 [1].
• Thus, PRMT6 can compromise Tat transcriptional activation and may represent a form of innate cellular immunity in regard to HIV-1 replication [1].
• The polypeptide chain of PRMT6 is 41.9 kDa consisting of a catalytic core sequence common to other PRMT enzymes [4].
• In searching the human genome for protein arginine N-methyltransferase (PRMT) family members, a novel gene has been found on chromosome 1 that encodes for an apparent methyltransferase, PRMT6 [4].
• 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 [7].

Regulatory relationships of PRMT6

• Using a TSP-1 promoter reporter gene, we further show that PRMT6 directly regulates the TSP-1 promoter activity [8].

References