Open Access

Archishman Ghosh, Advait Thatte, Surased Suraritdechachai, Roman Rattunde, Christoph A. Weber, T.-Y. Dora Tang

• We show that coupling enzymatic activity to condensation under limited resource conditions drives emergent self-regulation via droplet formation and dissolution. Our kinetic models show that in situ phase separation of in-vitro-transcribed mRNA with an intrinsically disordered protein (mutant G3BP1) modulates transcription and degradation kinetics. When resources for mRNA production are limited, condensates spontaneously dissolve, driven by the feedback from compartmentalization on reaction rate constants—with slower degradation within condensates than in the mRNA-protein-poor phase. Consequently, the lifetime of mRNA is prolonged upon condensation compared to the case without condensates. Extending the model to sustained and oscillatory resource supply reveals that condensates elevate mean mRNA levels and buffer deviations from the mean compared to the non-condensate scenario. These findings provide a general mechanism of cross-regulation and feedback between phase separation andWe show that coupling enzymatic activity to condensation under limited resource conditions drives emergent self-regulation via droplet formation and dissolution. Our kinetic models show that in situ phase separation of in-vitro-transcribed mRNA with an intrinsically disordered protein (mutant G3BP1) modulates transcription and degradation kinetics. When resources for mRNA production are limited, condensates spontaneously dissolve, driven by the feedback from compartmentalization on reaction rate constants—with slower degradation within condensates than in the mRNA-protein-poor phase. Consequently, the lifetime of mRNA is prolonged upon condensation compared to the case without condensates. Extending the model to sustained and oscillatory resource supply reveals that condensates elevate mean mRNA levels and buffer deviations from the mean compared to the non-condensate scenario. These findings provide a general mechanism of cross-regulation and feedback between phase separation and enzymatic reactions, highlighting condensates as active regulators of biochemical flux rather than as passive organizers.…