Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations

Nikolic, Nela and Bergmiller, Tobias and Vandervelde, Alexandra and Albanese, Tanino G and Gelen, Lendert and Moll, Isabella (2018) Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. Article number: gky079. ISSN 0305-1048

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The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin-antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress.

Item Type: Article
DOI: 10.1093/nar/gky079
Subjects: 500 Science > 570 Life sciences; biology > 576 Genetics and evolution
Research Group: Guet Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 20 Feb 2018 07:28
Last Modified: 20 Feb 2018 07:28

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