RNA synthesis and degradation regulate biomolecular condensates through non-equilibrium feedback
Sanchez-Burgos, I.; Tejedor, A. R.; Ocana, A.; R. Espinosa, J.; Collepardo-Guevara, R.
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Transcriptional condensates operate far from equilibrium, where continuous RNA synthesis and degradation dynamically reshape condensate composition. To investigate how RNA synthesis regulates condensate properties at sub-molecular resolution, we introduce REACT-RNA, a chemically specific coarse-grained molecular dynamics framework that explicitly couples RNA polymerisation, degradation, and nucleotide fluxes to sequence-dependent protein-RNA phase behaviour. Using FUS and MED1 as model systems, we show that RNA growth remodels condensate phase behaviour by altering RNA length distributions and intermolecular connectivity. Sustained RNA polymerisation drives re-entrant condensate dissolution, even of aged gel-like condensates, whereas RNA degradation stabilises long-lived non-equilibrium condensates containing excess RNA and negative charge beyond that tolerated at equilibrium. Our results suggest that RNA synthesis, degradation, and nucleotide fluxes drive transcriptional condensates out of thermodynamic equilibrium while condensates in turn promote reactive molecular configurations that favour RNA production, enabling transient accumulation of excess RNA and negative charge beyond equilibrium electroneutrality constraints during bursts of transcription.
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