Abstract

Protein arginine methyltransferases (PRMTs) function in the alkaline milieu of the nucleus and at neutral pH of the cytosol. Accordingly, several PRMTs are broadly active over a range of pHs. We investigated the effect altering pH had on protein arginine methylation using a variety of defined substrates, recombinant PRMTs and cell extracts.We demonstrate that pH-induced alterations in the extent of methylation and the methyl-product formed depend both on the particular substrate assayed and the PRMT that modifies it. We also find that transient intracellular alkalinization of mouse embryonic P19 neurons by NH₄Cl results in sustained changes in substrate methylation.  Altogether our results are consistent with a hypothesis in which altered substrate methylation resulting from pH-induced changes of PRMT activities coupled with low levels of demethylation may provide the long-term tag(s) necessary for the formation and maintenance of “molecular memory”.

Key words: Arginine methylation, protein arginine methyltransferase, pH, P19 cells, insect cell lysate, SmD1 peptide.