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Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns.

S Elizabeth Norred1,2, Patrick M Caveney1,2, Gaurav Chauhan3

  • 1Center for Nanophase Materials Sciences , Oak Ridge National Laboratory , Oak Ridge , Tennessee 37831 , United States.

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Summary

Macromolecular crowding increases protein noise in gene expression by creating spatial mRNA variations, impacting burst size and temporal fluctuations. This reveals how cellular crowding influences gene expression dynamics.

Keywords:
GUVcell-freegene expression burstinggene expression noiseliposomesmacromolecular crowding

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Area of Science:

  • Molecular and Cellular Biology
  • Biophysics
  • Synthetic Biology

Background:

  • Cytoplasmic macromolecular crowding in E. coli creates local concentration variations, influencing molecular transport and gene expression.
  • Gene expression bursting, characterized by episodic mRNA and protein production, is a key cellular process.
  • The specific impact of macromolecular crowding on gene expression bursting dynamics remains largely unexplored.

Purpose of the Study:

  • To investigate how macromolecular crowding affects the relationship between mRNA and protein population statistics during gene expression bursting.
  • To elucidate the role of spatial inhomogeneities in mediating the effects of crowding on protein production variability.

Main Methods:

  • Simultaneous measurement of mRNA and protein reporters in cell-free systems.
  • Experimental manipulation of macromolecular crowding conditions to mimic cellular environments.
  • Analysis of population statistics, noise, and spatial distribution of mRNA and protein.

Main Results:

  • Macromolecular crowding decoupled the typical relationship between mRNA and protein population fluctuations.
  • Crowded conditions increased protein noise by 10-fold, despite modest changes in mRNA statistics.
  • Crowding induced spatial mRNA noise, leading to significant variability in protein production burst size and temporal fluctuations.

Conclusions:

  • Macromolecular crowding significantly impacts gene expression bursting dynamics by creating spatial inhomogeneities in mRNA distribution.
  • Spatial mRNA noise, driven by crowding, is a key factor in generating large temporal fluctuations in protein production.
  • Findings offer insights into leveraging crowding-induced organizational principles for synthetic biology applications.