RNA Synthesis and Degradation Regulate Biomolecular Condensates through Nonequilibrium Feedback
5 affiliations
- 1University of Cambridge , , Lensfield Road , ,
- 2Universidad Complutense de Madrid , , Av. Complutense s/n , ,
- 3PhAsIca Biosciences S.L. , Calle Velázquez, 27 , ,
- 4Complutense University of Madrid , , Paseo Juan XXIII, 1 , ,
- 5University of Cambridge , , ,
Abstract
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 submolecular resolution, we introduce REACT-RNA, a chemically specific coarse-grained molecular dynamics framework that explicitly couples RNA polymerization, degradation, and nucleotide fluxes to sequence-dependent protein–RNA phase behavior and apply it to FUS and MED1 condensates. We find that RNA polymerization occurs preferentially at condensate interfaces because interfaces promote a highly reactive microenvironment that combines nucleotide influx, enrichment of reactive RNA chain ends, and enhanced molecular dynamics. Interfacial RNA polymerization generates a spatially organized RNA population, with newly synthesized short RNAs enriched near the interface and longer RNAs partitioning toward the condensate core, which decreases the interfacial free energy and promotes multivalent RNA–protein interactions. As RNA concentration and chain length evolve over time, condensate composition, density, and stability change dynamically in response. Sustained RNA polymerization drives re-entrant condensate dissolution, even of aged gel-like condensates, whereas RNA degradation stabilizes long-lived nonequilibrium condensates containing elevated RNA content. 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 favor RNA production, enabling transient accumulation of RNA-rich compositional imbalance during bursts of transcription.
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BibTeX
@article{sanchezburgos2026synthesis,
title = {{RNA Synthesis and Degradation Regulate Biomolecular Condensates through Nonequilibrium Feedback}},
author = {Ignacio Sanchez-Burgos and Andrés R. Tejedor and Alberto Ocana and Jorge R. Espinosa and Rosana Collepardo-Guevara},
journal = {ACS Central Science},
year = {2026},
month = oct,
doi = {10.1021/acscentsci.6c00933},
url = {https://pubs.acs.org/acscii/article/12/10/1672/5445324/RNA-Synthesis-and-Degradation-Regulate},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RNA Synthesis and Degradation Regulate Biomolecular Condensates through Nonequilibrium Feedback
AU - Ignacio Sanchez-Burgos
AU - Andrés R. Tejedor
AU - Alberto Ocana
AU - Jorge R. Espinosa
AU - Rosana Collepardo-Guevara
PY - 2026
DA - 2026/10/06
JO - ACS Central Science
DO - 10.1021/acscentsci.6c00933
UR - https://pubs.acs.org/acscii/article/12/10/1672/5445324/RNA-Synthesis-and-Degradation-Regulate
AB - 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 submolecular resolution, we introduce REACT-RNA, a chemically specific coarse-grained molecular dynamics framework that explicitly couples RNA polymerization, degradation, and nucleotide fluxes to sequence-dependent protein–RNA phase behavior and apply it to FUS and MED1 condensates. We find that RNA polymerization occurs preferentially at condensate interfaces because interfaces promote a highly reactive microenvironment that combines nucleotide influx, enrichment of reactive RNA chain ends, and enhanced molecular dynamics. Interfacial RNA polymerization generates a spatially organized RNA population, with newly synthesized short RNAs enriched near the interface and longer RNAs partitioning toward the condensate core, which decreases the interfacial free energy and promotes multivalent RNA–protein interactions. As RNA concentration and chain length evolve over time, condensate composition, density, and stability change dynamically in response. Sustained RNA polymerization drives re-entrant condensate dissolution, even of aged gel-like condensates, whereas RNA degradation stabilizes long-lived nonequilibrium condensates containing elevated RNA content. 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 favor RNA production, enabling transient accumulation of RNA-rich compositional imbalance during bursts of transcription.
SN - 2374-7943
SN - 2374-7951
ER -