Change in inorganic phosphate physical state can regulate transcription

Inorganic phosphate (P_i), a ubiquitous metabolite, is involved in all major biochemical pathways. We demonstrate that, in vitro, MgHPO₄ (the intracellular P_i 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 P_i on transcription in vivo will, therefore, reflect the physical state of intracellular P_i.