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

Singhroy DN, Mesplède T, Sabbah A, Quashie PK, Falgueyret JP, Wainberg MA - Retrovirology (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill University AIDS Centre, Lady Davis for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine, Montreal, QC, H3T 1E2, Canada.

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.

Show MeSH
The R35 residue is conserved in evolution. Sequence alignment of PRMT6 proteins from various organisms showing conservation of the arginine residue at position 35 (H. sapiens). The consensus sequence was produced using ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/). R35 is bolded and the underlined text refers to the arginine rich motif.
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Figure 2: The R35 residue is conserved in evolution. Sequence alignment of PRMT6 proteins from various organisms showing conservation of the arginine residue at position 35 (H. sapiens). The consensus sequence was produced using ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/). R35 is bolded and the underlined text refers to the arginine rich motif.

Mentions: Alignment studies show that the R35, R37, and R38 residues are well conserved among mammals e.g. Homo sapiens, Pan troglodytes, Macaca mulatta, Sus scrofa, Mus musculus, Rattus norvegicus, and Bos Taurus (Figure 2), but the region is not conserved in some other organisms, e.g. Arabidopsis thaliana and Danio rerio (data not shown), suggesting that its emergence followed the divergence that occurred between these branches in evolution. R29 is poorly evolutionary conserved.


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

Singhroy DN, Mesplède T, Sabbah A, Quashie PK, Falgueyret JP, Wainberg MA - Retrovirology (2013)

The R35 residue is conserved in evolution. Sequence alignment of PRMT6 proteins from various organisms showing conservation of the arginine residue at position 35 (H. sapiens). The consensus sequence was produced using ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/). R35 is bolded and the underlined text refers to the arginine rich motif.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750301&req=5

Figure 2: The R35 residue is conserved in evolution. Sequence alignment of PRMT6 proteins from various organisms showing conservation of the arginine residue at position 35 (H. sapiens). The consensus sequence was produced using ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/). R35 is bolded and the underlined text refers to the arginine rich motif.
Mentions: Alignment studies show that the R35, R37, and R38 residues are well conserved among mammals e.g. Homo sapiens, Pan troglodytes, Macaca mulatta, Sus scrofa, Mus musculus, Rattus norvegicus, and Bos Taurus (Figure 2), but the region is not conserved in some other organisms, e.g. Arabidopsis thaliana and Danio rerio (data not shown), suggesting that its emergence followed the divergence that occurred between these branches in evolution. R29 is poorly evolutionary conserved.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: McGill University AIDS Centre, Lady Davis for Medical Research, Jewish General Hospital, 3755 Cote Sainte Catherine, Montreal, QC, H3T 1E2, Canada.

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.

Show MeSH