Change in inorganic phosphate physical state can regulate transcription

ABSTRACT Inorganic phosphate (Pi), a ubiquitous metabolite, is involved in all major biochemical pathways. We demonstrate that, in vitro, MgHPO4 (the intracellular Pi form) at physiological concentrations can exist in a metastable supersaturated dissolved state or as a precipitate. We have shown that in solution, MgHPO4 strongly stimulates exonuclease nascent transcript cleavage by RNA polymerase. We report here that MgHPO4 precipitate selectively and efficiently inhibits transcription initiation in vitro. In view of the MgHPO4 solubility and in vitro sensitivity of RNA synthesis to MgHPO4 precipitate, at physiological concentrations, MgHPO4 should cause a 50–98% inhibition of cellular RNA synthesis, thus exerting a strong regulatory action. The effects of Pi on transcription in vivo will, therefore, reflect the physical state of intracellular Pi.