Protein arginine methyltransferase 1-directed methylation of Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen. – PubMed

Protein arginine methyltransferase 1-directed methylation of Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen. - PubMed

Protein arginine methyltransferase 1-directed methylation of Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen. - PubMed
THE replication of several DNA viruses including Marek’s disease herpesvirus (MDHV) is largely dependent on the presence of arginine in the medium1–5 . Post-translational modification of LANA is important for functional diversification. ICP27 contains an RGG box and has been shown to be methylated during viral infection. The major arginine methylation site in LANA was mapped to arginine 20. 12), were that they appeared on the surface of infected cells as an early product of the viral genome and that DNA inhibitors did not prevent their formation, whereas protein inhibitors did so completely. The significance of the methylation in LANA function was examined in both the isolated form and in the context of the viral genome through the generation of recombinant KSHV. Most striking was the finding that under conditions of hypomethylation resulting from infection with arginine substitution mutants or treatment of wild-type HSV-1-infected cells with the methylation inhibitor adenosine dialdehyde, ICP27 export to the cytoplasm occurred earlier and was more rapid than wild-type ICP27 export.

Although mutation of the methylation site resulted in no significant difference in KSHV LANA subcellular localization, we found that the methylation mimetic mutation resulted in augmented histone binding in vitro and increased LANA occupancy at identified LANA target promoters in vivo. W. These results suggest that residue 20 is important for modulation of a subset of LANA functions and properties of this residue, including the hydrophobic character induced by arginine methylation, may contribute to the observed effects.

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