A conserved thermodynamic signature links transcriptome organization to growth state

Thermodynamic principles govern living systems, maintaining complexity through ongoing free-energy intake and heat release. However, the broader functional constraints arising from non-equilibrium dynamics are not yet fully understood. To understand how cellular entropy generation influences structure within the cell during transitions between proliferative states, researchers created a stochastic-thermodynamic model that links reduced dissipative drive to temporary boosts in intracellular configurational entropy.

In this context, the team investigated abundance-weighted predicted RNA folding stability as a potential method to represent the overall intracellular configurational rearrangement. The results aligned with the model, revealing that transcriptome rearrangement throughout the cell cycle results in synchronized, state-dependent alterations in the distribution of transcript-level RNA folding free energies.

When applied to stress adaptation, human cancer cells exposed to targeted medications and nutrient-deprived E. coli bacteria both exhibited expressed RNA pools enriched with transcripts featuring less negative RNA folding free energies. Despite considerable variability in the transcriptional responses within each system, this pattern persisted.

Similarly, opposing changes during acquired resistance in the presence of continuous drug exposure and bacterial recovery from starvation further reinforce the link between growth state and RNA organization. Collectively, these observations suggest that transcriptome organization transcends gene-regulatory mechanisms, encompassing collective biophysical properties that may embody non-equilibrium constraints guiding cellular-state transitions.