Change in inorganic phosphate physical state can regulate transcription

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Regulation

Background:

• Inorganic phosphate (Pi) is a vital metabolite in all major biochemical pathways.
• Magnesium hydrogen phosphate (MgHPO4), the intracellular form of Pi, exhibits dual states: a dissolved supersaturated solution or a precipitate at physiological concentrations.

Purpose of the Study:

• To investigate the impact of MgHPO4's physical state on RNA synthesis.
• To elucidate the regulatory role of intracellular phosphate in cellular processes.

Main Methods:

• In vitro experiments assessing MgHPO4's effect on RNA polymerase activity.
• Analysis of MgHPO4 solubility and its influence on transcription initiation and elongation.

Main Results:

• Dissolved MgHPO4 stimulates exonuclease-mediated nascent transcript cleavage by RNA polymerase.
• MgHPO4 precipitate selectively and potently inhibits transcription initiation in vitro.
• Calculations predict 50-98% inhibition of cellular RNA synthesis by MgHPO4 precipitate at physiological concentrations.

Conclusions:

• The physical state of intracellular inorganic phosphate (Pi) is critical for regulating cellular RNA synthesis.
• MgHPO4 precipitate acts as a potent inhibitor of transcription initiation, suggesting a significant regulatory mechanism.
• In vivo effects of Pi on transcription are dependent on whether Pi is in a dissolved or precipitated state.