Knockout of the Hmt1p Arginine Methyltransferase in Leads to the Dysregulation of Phosphate-associated Genes and Processes.

Hmt1p is the predominant arginine methyltransferase in Its substrate proteins are involved in transcription, transcriptional regulation, nucleocytoplasmic transport and RNA splicing. Hmt1p-catalyzed methylation can also modulate protein-protein interactions. Hmt1p is conserved from unicellular eukaryotes through to mammals where its ortholog, PRMT1, is lethal upon knockout. In yeast, however, the effect of knockout on the transcriptome and proteome has not been described. Transcriptome analysis revealed downregulation of phosphate-responsive genes in Δ, including acid phosphatases , , and , phosphate transporters and and the vacuolar transporter chaperone Analysis of the Δ proteome revealed decreased abundance of phosphate-associated proteins including phosphate transporter Pho84p, vacuolar alkaline phosphatase Pho8p, acid phosphatase Pho3p and subunits of the vacuolar transporter chaperone complex Vtc1p, Vtc3p and Vtc4p. Consistent with this, phosphate homeostasis was dysregulated in Δ cells, showing decreased extracellular phosphatase levels and decreased total P in phosphate-depleted medium. , we showed that transcription factor Pho4p can be methylated at Arg-241, which could explain phosphate dysregulation in Δ if interplay exists with phosphorylation at Ser-242 or Ser-243, or if Arg-241 methylation affects the capacity of Pho4p to homodimerize or interact with Pho2p. However, the Arg-241 methylation site was not validated and the localization of a Pho4p-GFP fusion in Δ was not different from wild type. To our knowledge, this is the first study to reveal an association between Hmt1p and phosphate homeostasis and one which suggests a regulatory link between S-adenosyl methionine and intracellular phosphate.