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Open AccessArticle

Transcriptomics Unveil Canonical and Non-Canonical Heat Shock-Induced Pathways in Human Cell Lines

by Andrew Reinschmidt, Luis Solano, Yonny Chavez, William Drew Hulsy and Nikolas Nikolaidis

Int. J. Mol. Sci. 2025, 26(3), 1057; https://doi.org/10.3390/ijms26031057 - 26 Jan 2025

Cited by 4 | Viewed by 2460

The cellular stress response (CSR) is a conserved mechanism that protects cells from -environmental and physiological stressors. The heat shock response (HSR), a critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic stress caused by elevated temperatures. We hypothesized that while the canonical HSR pathways are conserved across cell types, specific cell lines may exhibit unique transcriptional responses to heat shock. To test this, we compared the transcriptomic responses of HEK293, HepG2, and HeLa cells under control conditions immediately following heat shock and after an 8-h recovery period. RNA sequencing revealed the conserved activation of canonical HSR pathways, including the unfolded protein response, alongside the -enrichment of the non-canonical “Receptor Ligand Activity” pathway across all cell lines. Cell-line-specific variations were observed, with HepG2 cells exhibiting significantly higher ex-pression levels of certain genes compared to other cell lines under stress conditions, as well as greater fold changes in gene expression relative to its control conditions. Validation by qPCR confirmed the activation of key genes within the “Receptor Ligand Activity” pathway across time points. These findings provide insights into conserved and context-specific aspects of the HSR, contributing to a more comprehensive understanding of stress response mechanisms across mammalian cells. Full article

(This article belongs to the Collection Feature Papers in Molecular Biophysics)

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25 pages, 5223 KB

Open AccessEditor’s ChoiceArticle

The Post-Transcriptional Regulatory Protein CsrA Amplifies Its Targetome through Direct Interactions with Stress-Response Regulatory Hubs: The EvgA and AcnA Cases

by Alejandra Matsuri Rojano-Nisimura, Kobe B. Grismore, Josie S. Ruzek, Jacqueline L. Avila and Lydia M. Contreras

Microorganisms 2024, 12(4), 636; https://doi.org/10.3390/microorganisms12040636 - 22 Mar 2024

Cited by 5 | Viewed by 4048

Abstract

Global rewiring of bacterial gene expressions in response to environmental cues is mediated by regulatory proteins such as the CsrA global regulator from E. coli. Several direct mRNA and sRNA targets of this protein have been identified; however, high-throughput studies suggest an expanded RNA targetome for this protein. In this work, we demonstrate that CsrA can extend its network by directly binding and regulating the evgA and acnA transcripts, encoding for regulatory proteins. CsrA represses EvgA and AcnA expression and disrupting the CsrA binding sites of evgA and acnA, results in broader gene expression changes to stress response networks. Specifically, altering CsrA-evgA binding impacts the genes related to acidic stress adaptation, and disrupting the CsrA-acnA interaction affects the genes involved in metal-induced oxidative stress responses. We show that these interactions are biologically relevant, as evidenced by the improved tolerance of evgA and acnA genomic mutants depleted of CsrA binding sites when challenged with acid and metal ions, respectively. We conclude that EvgA and AcnA are intermediate regulatory hubs through which CsrA can expand its regulatory role. The indirect CsrA regulation of gene networks coordinated by EvgA and AcnA likely contributes to optimizing cellular resources to promote exponential growth in the absence of stress. Full article

(This article belongs to the Special Issue Bacterial Stress Response Mechanisms: Signal Perception, Transduction and Adaptation 2.0)

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20 pages, 3714 KB

Open AccessArticle

CsrA Regulates Swarming Motility and Carbohydrate and Amino Acid Metabolism in Vibrio alginolyticus

by Bing Liu, Qian Gao, Xin Zhang, Huizhen Chen, Ying Zhang, Yuehong Sun, Shan Yang and Chang Chen

Microorganisms 2021, 9(11), 2383; https://doi.org/10.3390/microorganisms9112383 - 18 Nov 2021

Cited by 15 | Viewed by 4189

Abstract

Vibrio alginolyticus, like other vibrio species, is a widely distributed marine bacterium that is able to outcompete other species in variable niches where diverse organic matters are supplied. However, it remains unclear how these cells sense and adjust metabolic flux in response to the changing environment. CsrA is a conserved RNA-binding protein that modulates critical cellular processes such as growth ability, central metabolism, virulence, and the stress response in gamma-proteobacteria. Here, we first characterize the csrA homolog in V. alginolyticus. The results show that CsrA activates swarming but not swimming motility, possibly by enhancing the expression of lateral flagellar associated genes. It is also revealed that CsrA modulates the carbon and nitrogen metabolism of V. alginolyticus, as evidenced by a change in the growth kinetics of various carbon and nitrogen sources when CsrA is altered. Quantitative RT-PCR shows that the transcripts of the genes encoding key enzymes involved in the TCA cycle and amino acid metabolism change significantly, which is probably due to the variation in mRNA stability given by CsrA binding. This may suggest that CsrA plays an important role in sensing and responding to environmental changes. Full article

(This article belongs to the Special Issue Bacterial Responses to Environmental Stress and Their Specific Contribution to Escherichia coli and Vibrio spp. Survival and Virulence 2.0)

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