Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival

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.

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Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival

10.1101/212902 ◽

2017 ◽

Cited By ~ 2

Author(s):

Matthew Z. Tien ◽

Aretha Fiebig ◽

Sean Crosson

Keyword(s):

Gene Expression ◽

Caulobacter Crescentus ◽

Transcriptional Regulator ◽

Functional Roles ◽

Large Gene ◽

Stress Survival ◽

Gene Network Analysis ◽

Catalase Peroxidase ◽

Necessary And Sufficient ◽

Transcription Data

SUMMARYCells 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 transcription data to predict genes that serve major functional roles inCaulobacter crescentusstress survival. This approach identified GsrN, a conserved small RNA that is directly controlled by the general stress sigma factor, στ, and functions as a potent post-transcriptional regulator of survival under multiple stress conditions. GsrN expression is both necessary and sufficient to protect cells from hydrogen peroxide, where it functions by base pairing with the leader ofkatGmRNA and promoting catalase/peroxidase expression. We conclude that GsrN convenes a post-transcriptional layer of gene expression that serves a central functional role in stress physiology.

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ADAGE-Based Integration of Publicly Available Pseudomonas aeruginosa Gene Expression Data with Denoising Autoencoders Illuminates Microbe-Host Interactions

mSystems ◽

10.1128/msystems.00025-15 ◽

2016 ◽

Vol 1 (1) ◽

Cited By ~ 57

Author(s):

Jie Tan ◽

John H. Hammond ◽

Deborah A. Hogan ◽

Casey S. Greene

Keyword(s):

Gene Expression ◽

Pseudomonas Aeruginosa ◽

Source Code ◽

Biological Knowledge ◽

Data Sets ◽

Data Types ◽

Content Type ◽

Gene Pathway ◽

Large Gene ◽

Genome Scale

ABSTRACT The quantity and breadth of genome-scale data sets that examine RNA expression in diverse bacterial and eukaryotic species are increasing more rapidly than for curated knowledge. Our ADAGE method integrates such data without requiring gene function, gene pathway, or experiment labeling, making practical its application to any large gene expression compendium. We built a Pseudomonas aeruginosa ADAGE model from a diverse set of publicly available experiments without any prespecified biological knowledge, and this model was accurate and predictive. We provide ADAGE results for the complete P. aeruginosa GeneChip compendium for use by researchers studying P. aeruginosa and source code that facilitates ADAGE’s application to other species and data types. The increasing number of genome-wide assays of gene expression available from public databases presents opportunities for computational methods that facilitate hypothesis generation and biological interpretation of these data. We present an unsupervised machine learning approach, ADAGE (analysis using denoising autoencoders of gene expression), and apply it to the publicly available gene expression data compendium for Pseudomonas aeruginosa. In this approach, the machine-learned ADAGE model contained 50 nodes which we predicted would correspond to gene expression patterns across the gene expression compendium. While no biological knowledge was used during model construction, cooperonic genes had similar weights across nodes, and genes with similar weights across nodes were significantly more likely to share KEGG pathways. By analyzing newly generated and previously published microarray and transcriptome sequencing data, the ADAGE model identified differences between strains, modeled the cellular response to low oxygen, and predicted the involvement of biological processes based on low-level gene expression differences. ADAGE compared favorably with traditional principal component analysis and independent component analysis approaches in its ability to extract validated patterns, and based on our analyses, we propose that these approaches differ in the types of patterns they preferentially identify. We provide the ADAGE model with analysis of all publicly available P. aeruginosa GeneChip experiments and open source code for use with other species and settings. Extraction of consistent patterns across large-scale collections of genomic data using methods like ADAGE provides the opportunity to identify general principles and biologically important patterns in microbial biology. This approach will be particularly useful in less-well-studied microbial species. IMPORTANCE The quantity and breadth of genome-scale data sets that examine RNA expression in diverse bacterial and eukaryotic species are increasing more rapidly than for curated knowledge. Our ADAGE method integrates such data without requiring gene function, gene pathway, or experiment labeling, making practical its application to any large gene expression compendium. We built a Pseudomonas aeruginosa ADAGE model from a diverse set of publicly available experiments without any prespecified biological knowledge, and this model was accurate and predictive. We provide ADAGE results for the complete P. aeruginosa GeneChip compendium for use by researchers studying P. aeruginosa and source code that facilitates ADAGE’s application to other species and data types. Author Video: An author video summary of this article is available.

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Author response: Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival

10.7554/elife.33684.044 ◽

2018 ◽

Author(s):

Matthew Tien ◽

Aretha Fiebig ◽

Sean Crosson

Keyword(s):

Network Analysis ◽

Gene Network ◽

Cellular Stress ◽

Transcriptional Regulator ◽

Author Response ◽

Response Gene ◽

Stress Survival ◽

Gene Network Analysis

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Role and regulation of ferritin-like proteins in iron homeostasis and oxidative stress survival of Caulobacter crescentus

BioMetals ◽

10.1007/s10534-016-9956-y ◽

2016 ◽

Vol 29 (5) ◽

pp. 851-862 ◽

Cited By ~ 5

Author(s):

Ivan Gonçalves de Castro Ferreira ◽

Mirian Molnar Rodrigues ◽

José Freire da Silva Neto ◽

Ricardo Ruiz Mazzon ◽

Marilis do Valle Marques

Keyword(s):

Oxidative Stress ◽

Iron Homeostasis ◽

Caulobacter Crescentus ◽

Stress Survival ◽

And Oxidative Stress

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Decision letter: Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival

10.7554/elife.33684.043 ◽

2018 ◽

Keyword(s):

Network Analysis ◽

Gene Network ◽

Cellular Stress ◽

Transcriptional Regulator ◽

Stress Survival ◽

Gene Network Analysis

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Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽

10.3390/cancers13020350 ◽

2021 ◽

Vol 13 (2) ◽

pp. 350

Author(s):

Julianty Frost ◽

Mark Frost ◽

Michael Batie ◽

Hao Jiang ◽

Sonia Rocha

Keyword(s):

Gene Expression ◽

Hypoxia Inducible Factor ◽

Transcriptional Regulator ◽

Hydroxylase Activity ◽

Control Of Gene Expression ◽

Prolyl Hydroxylases ◽

Chromatin Organisation ◽

Sense And Respond ◽

Almost All ◽

And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

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YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

Cell Death Discovery ◽

10.1038/s41420-021-00609-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jie Mei ◽

Yan Liu ◽

Xinqian Yu ◽

Leiyu Hao ◽

Tao Ma ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Molecular Mechanisms ◽

Transcriptional Regulator ◽

Expression Levels ◽

Functional Roles ◽

Normal Tissues ◽

Rhoa Activation ◽

Promote Cell Migration

AbstractDishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

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Targeting ROS/NF-κB sigaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

Scientific Reports ◽

10.1038/s41598-021-96008-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Noha H. Habashy ◽

Ahmad S. Kodous ◽

Marwa M. Abu-Serie

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Vitis Vinifera ◽

Rat Kidney ◽

Environmental Pollutant ◽

Enhancing Effect ◽

Tnf Α ◽

Cox 2 ◽

Histopathological Studies ◽

And Oxidative Stress

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

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