Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival
- University of Chicago, United States
Abstract
Cells adapt to shifts in their environment by remodeling transcription. Measuring changes in transcription at the genome scale is now routine, but defining the functional significance of individual genes within large gene expression datasets remains a major challenge. We applied a network-based algorithm to interrogate publicly available gene expression data to predict genes that serve major functional roles in Caulobacter crescentus stress survival. This approach identified GsrN, a conserved small RNA that is directly activated by the general stress sigma factor, σT, and functions as a potent post-transcriptional regulator of survival across distinct conditions including osmotic and oxidative stress. Under hydrogen peroxide stress, GsrN protects cells by base pairing with the leader of katG mRNA and activating expression of KatG catalase/peroxidase protein. We conclude that GsrN convenes a post-transcriptional layer of gene expression that serves a central functional role in Caulobacter stress physiology.
Data availability
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RNA-Seq gene expression analysis of ΔgsrN, gsrN-OE, and wild-type Caulobacter crescentusPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106168).
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Identification of RNAs that co-purify with the Caulobacter sRNA, GsrNPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106171).
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Transcriptomic and phylogenetic analysis of a bacterial cell cycle reveals strong associations between gene co-expression and evolutionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE46915).
Article and author information
Author details
Funding
National Institutes of Health (1R01GM087353)
- Sean Crosson
National Institutes of Health (U19AI107792)
- Sean Crosson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Tien et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival
eLife 7:e33684.
https://doi.org/10.7554/eLife.33684
Further reading
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- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
Teichoic acids (TA) are linear phospho-saccharidic polymers and important constituents of the cell envelope of Gram-positive bacteria, either bound to the peptidoglycan as wall teichoic acids (WTA) or to the membrane as lipoteichoic acids (LTA). The composition of TA varies greatly but the presence of both WTA and LTA is highly conserved, hinting at an underlying fundamental function that is distinct from their specific roles in diverse organisms. We report the observation of a periplasmic space in Streptococcus pneumoniae by cryo-electron microscopy of vitreous sections. The thickness and appearance of this region change upon deletion of genes involved in the attachment of TA, supporting their role in the maintenance of a periplasmic space in Gram-positive bacteria as a possible universal function. Consequences of these mutations were further examined by super-resolved microscopy, following metabolic labeling and fluorophore coupling by click chemistry. This novel labeling method also enabled in-gel analysis of cell fractions. With this approach, we were able to titrate the actual amount of TA per cell and to determine the ratio of WTA to LTA. In addition, we followed the change of TA length during growth phases, and discovered that a mutant devoid of LTA accumulates the membrane-bound polymerized TA precursor.
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- Biochemistry and Chemical Biology
- Computational and Systems Biology
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