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Title: Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns

Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting—the episodic process where mRNA and proteins are produced in bursts. Here, we simultaneously measured mRNA and protein reporters in cell-free systems, showing that macromolecular crowding decoupled the well-known relationship between fluctuations in the protein population (noise) and mRNA population statistics. Crowded environments led to a 10-fold increase in protein noise even though there were only modest changes in the mRNA population and fluctuations. Instead, cell-like macromolecular crowding created an inhomogeneous spatial distribution of mRNA (“spatial noise”) that led to large variability in the protein production burst size. As a result, the mRNA spatial noise created large temporal fluctuations in the protein population. Furthermore, these results highlight the interplay between macromolecular crowding, spatial inhomogeneities, and the resulting dynamics of gene expression, and provide insights into using these organizational principles in both cell-based and cell-free synthetic biology.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [3] ; ORCiD logo [3] ;  [2] ; ORCiD logo [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Grant/Contract Number:
AC05-00OR22725
Type:
Accepted Manuscript
Journal Name:
ACS Synthetic Biology
Additional Journal Information:
Journal Volume: 7; Journal Issue: 5; Journal ID: ISSN 2161-5063
Publisher:
American Chemical Society (ACS)
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cell-free; gene expression bursting; gene expression noise; GUV; liposomes; macromolecular crowding
OSTI Identifier:
1439942

Norred, Sarah Elizabeth, Caveney, Patrick M., Chauhan, Gaurav, Collier, Lauren K., Collier, C. Patrick, Abel, Steven M., and Simpson, Michael L.. Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns. United States: N. p., Web. doi:10.1021/acssynbio.8b00139.
Norred, Sarah Elizabeth, Caveney, Patrick M., Chauhan, Gaurav, Collier, Lauren K., Collier, C. Patrick, Abel, Steven M., & Simpson, Michael L.. Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns. United States. doi:10.1021/acssynbio.8b00139.
Norred, Sarah Elizabeth, Caveney, Patrick M., Chauhan, Gaurav, Collier, Lauren K., Collier, C. Patrick, Abel, Steven M., and Simpson, Michael L.. 2018. "Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns". United States. doi:10.1021/acssynbio.8b00139.
@article{osti_1439942,
title = {Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns},
author = {Norred, Sarah Elizabeth and Caveney, Patrick M. and Chauhan, Gaurav and Collier, Lauren K. and Collier, C. Patrick and Abel, Steven M. and Simpson, Michael L.},
abstractNote = {Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting—the episodic process where mRNA and proteins are produced in bursts. Here, we simultaneously measured mRNA and protein reporters in cell-free systems, showing that macromolecular crowding decoupled the well-known relationship between fluctuations in the protein population (noise) and mRNA population statistics. Crowded environments led to a 10-fold increase in protein noise even though there were only modest changes in the mRNA population and fluctuations. Instead, cell-like macromolecular crowding created an inhomogeneous spatial distribution of mRNA (“spatial noise”) that led to large variability in the protein production burst size. As a result, the mRNA spatial noise created large temporal fluctuations in the protein population. Furthermore, these results highlight the interplay between macromolecular crowding, spatial inhomogeneities, and the resulting dynamics of gene expression, and provide insights into using these organizational principles in both cell-based and cell-free synthetic biology.},
doi = {10.1021/acssynbio.8b00139},
journal = {ACS Synthetic Biology},
number = 5,
volume = 7,
place = {United States},
year = {2018},
month = {4}
}