Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity

Retrovirology. 2013 Jul 17;10:73. doi: 10.1186/1742-4690-10-73.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry
  • Arginine / genetics
  • Arginine / metabolism
  • Cell Line
  • Chromatography, Liquid
  • Enzyme Stability
  • HIV-1 / immunology*
  • Humans
  • Mass Spectrometry
  • Methylation
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism*
  • Protein Processing, Post-Translational*
  • Protein-Arginine N-Methyltransferases / chemistry
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / immunology*
  • Protein-Arginine N-Methyltransferases / metabolism*

Substances

  • Mutant Proteins
  • Nuclear Proteins
  • Arginine
  • PRMT6 protein, human
  • Protein-Arginine N-Methyltransferases