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. 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.

journal_name

Retrovirology

journal_title

Retrovirology

authors

Singhroy DN,Mesplède T,Sabbah A,Quashie PK,Falgueyret JP,Wainberg MA

doi

10.1186/1742-4690-10-73

subject

Has Abstract

pub_date

2013-07-17 00:00:00

pages

73

issn

1742-4690

pii

1742-4690-10-73

journal_volume

10

pub_type

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