Enzymatic methylation of heterogeneous nuclear ribonucleoprotein in isolated liver nuclei.

Protein N-methyltransferase activity has been studied in the rat liver nuclei, using recombinant heterogeneous nuclear ribonucleoprotein particle protein A1 and histone as the methyl acceptors. The hydrolysates of these two enzymatically [methyl-3H]-labeled proteins, however, yielded different patterns of methylated amino acids on HPLC analysis: NG-monomethylarginine (92%) and NG-NG-dimethyl (asymmetric) arginine (6.5%) were the major methylated amino acids identified in the protein A1, whereas epsilon-N-methylated lysine derivatives constituted a predominant portion (71%) of the methylated amino acids in histone. When liver extracts isolated from rats fed a methyl deficient diet were assayed, the methyl accepting activity of protein A1 increased 64% over the control (rats fed normal diet), while that of histone increased 260%. Partial hepatectomy induced a 7.9-fold and 2.3-fold increase in the protein A1 methylase activity after 24 and 48 h of regeneration, respectively. These results, together with the fact that myelin basic protein-specific protein methylase I does not significantly methylate protein A1, indicate the presence of an enzyme in the rat liver nuclei which methylates the protein A1.