Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns

Norred, Sarah Elizabeth; Caveney, Patrick M.; Chauhan, Gaurav; Collier, Lauren K.; Collier, C. Patrick; Abel, Steven M.; Simpson, Michael L.

doi:10.1021/acssynbio.8b00139

Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns

Journal Article · Tue Apr 24 00:00:00 EDT 2018 · ACS Synthetic Biology

DOI:https://doi.org/10.1021/acssynbio.8b00139· OSTI ID:1439942

^[1]; Caveney, Patrick M. ^[1]; Chauhan, Gaurav ^[2]; Collier, Lauren K. ^[3]; ^[3]; Abel, Steven M. ^[2]; ^[1]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
Univ. of Tennessee, Knoxville, TN (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1439942

Journal Information:: ACS Synthetic Biology, Journal Name: ACS Synthetic Biology Journal Issue: 5 Vol. 7; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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