title: Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity.
abstract: BACKGROUND
  Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucleocapsid (NC). PRMT6 also displays automethylation capacity but the role of this post-translational modification in its antiretroviral activity remains unknown.
  
  
  RESULTS
  Here we report the identification by liquid chromatography-mass spectrometry of R35 within PRMT6 as the target residue for automethylation and have confirmed this by site-directed mutagenesis and in vitro and in vivo methylation assays. We further show that automethylation at position 35 greatly affects PRMT6 stability and is indispensable for its antiretroviral activity, as demonstrated in HIV-1 single-cycle TZM-bl infectivity assays.
  
  
  CONCLUSIONS
  These results show that PRMT6 automethylation plays a role in the stability of this protein and that this event is indispensible for its anti-HIV-1 activity.
authors.affiliation: McGill University AIDS Centre, Lady Davis for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine, Montreal, QC, H3T 1E2, Canada.
authors.forename: Diane N
authors.initials: DN
authors.lastname: Singhroy
authors.forename: Thibault
authors.initials: T
authors.lastname: Mesplède
authors.forename: Arielle
authors.initials: A
authors.lastname: Sabbah
authors.forename: Peter K
authors.initials: PK
authors.lastname: Quashie
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002853:Chromatography, Liquid; D004795:Enzyme Stability; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D013058:Mass Spectrometry; D008745:Methylation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D009687:Nuclear Proteins; D001120:Arginine; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases