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Liquid-liquid phase separation driven compartmentalization of reactive nucleoplasm.

Rabia Laghmach1,2,3, Davit A Potoyan1,2,3

  • 1Department of Chemistry, Iowa State University, Ames, IA 50011, United States of America.

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|October 28, 2020
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Gene regulation impacts nuclear order through biomolecular phase separation. Our model reveals how reaction kinetics and phase separation create varied gene expression patterns and condensate structures.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Systems Biology

Background:

  • Eukaryotic cell nuclei contain dynamic, non-equilibrium environments crucial for gene regulation.
  • Gene regulation occurs within compartmentalized sub-nuclear bodies, but the impact of gene regulation on nuclear order is less understood.
  • Liquid-liquid phase separation drives the formation of biomolecular condensates, influencing nuclear organization.

Purpose of the Study:

  • To investigate how gene regulation kinetically controls biomolecular phase separation within the nucleus.
  • To explore the relationship between gene expression dynamics and nuclear structure formation.
  • To develop a minimalist model of the reactive nucleoplasm.

Main Methods:

  • Constructed a minimalist model of the reactive nucleoplasm.
  • Employed the Cahn-Hilliard formulation for ternary protein-RNA-nucleoplasm components.
  • Coupled the model to non-equilibrium and spatially dependent gene expression simulations.

Main Results:

  • Identified diverse kinetic regimes governing phase separation and reaction timescales.
  • Demonstrated that the interplay generates heterogeneous, multi-modal gene expression patterns.
  • Linked gene expression heterogeneity directly to the heterogeneity of length scales in phase-separated condensates.

Conclusions:

  • Gene regulation actively influences nuclear order through kinetic control of phase separation.
  • The study provides a mechanistic link between dynamic gene expression and the formation of nuclear condensates.
  • Findings suggest that nuclear condensate heterogeneity reflects underlying gene expression heterogeneity.