Unknown,Transcriptomics,Genomics,Proteomics

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Contributions of transcription and mRNA turnover to gene expression dynamics of fission Yeast Extract mediumast in response to oxidative stress

ABSTRACT: The cooperation of transcriptional and post-transcriptional controls to shape gene regulation is poorly understood. Here we show that a combination of two simple and non-invasive genomic techniques, coupled with kinetic mathematical modelling, afford insight into the multi-layered regulation of gene expression dynamics in response to oxidative stress in the fission yeast Schizosaccharomyces pombe. This study reveals a dominant role of transcriptional control in response to stress, and it points to the first minutes after stress induction as a critical time when control of mRNA turnover can support transcriptional control for rapid gene regulation. In addition, we uncover specialized gene expression strategies such as simultaneous transcriptional repression and mRNA destabilization for genes encoding ribosomal proteins, delayed mRNA destabilization with varying contribution of transcription for the ribosome biogenesis regulon, dominant roles of mRNA stabilisation for genes participating in protein degradation, and adjustment of mRNA turnover during stress adaptation. We also show that genes regulated independently of the Atf1p transcription factor are mainly controlled by mRNA turnover during oxidative stress.

An additional file containing normalized data is available on the FTP site for this experiment.

ORGANISM(S): Schizosaccharomyces pombe

SUBMITTER: Samuel Marguerat

PROVIDER: E-MTAB-504 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Smith2013 - Regulation of Insulin Signalling by Oxidative Stress The model describes insulin signalling (in rodent adipocytes), which includes in addition to the core pathway, the transcriptional feedback through the Forkhead box type O (FOXO) transcription factor and interaction with oxidative stress. This model is described in the article: Computational modelling of the regulation of Insulin signalling by oxidative stress. Smith GR, Shanley DP. BMC Syst Biol. 2013 May 24;7:41. Abstract: BACKGROUND: Existing models of insulin signalling focus on short term dynamics, rather than the longer term dynamics necessary to understand many physiologically relevant behaviours. We have developed a model of insulin signalling in rodent adipocytes that includes both transcriptional feedback through the Forkhead box type O (FOXO) transcription factor, and interaction with oxidative stress, in addition to the core pathway. In the model Reactive Oxygen Species are both generated endogenously and can be applied externally. They regulate signalling though inhibition of phosphatases and induction of the activity of Stress Activated Protein Kinases, which themselves modulate feedbacks to insulin signalling and FOXO. RESULTS: Insulin and oxidative stress combined produce a lower degree of activation of insulin signalling than insulin alone. Fasting (nutrient withdrawal) and weak oxidative stress upregulate antioxidant defences while stronger oxidative stress leads to a short term activation of insulin signalling but if prolonged can have other effects including degradation of the insulin receptor substrate (IRS1) and FOXO. At high insulin the protective effect of moderate oxidative stress may disappear. CONCLUSION: Our model is consistent with a wide range of experimental data, some of which is difficult to explain. Oxidative stress can have effects that are both up- and down-regulatory on insulin signalling. Our model therefore shows the complexity of the interaction between the two pathways and highlights the need for such integrated computational models to give insight into the dysregulation of insulin signalling along with more data at the individual level.A complete SBML model file can be downloaded from BIOMODELS (https://www.ebi.ac.uk/biomodels-main) with unique identifier MODEL1212210000.Other files and scripts are available as additional files with this journal article and can be downloaded from https://github.com/graham1034/Smith2012_insulin_signalling. This model is hosted on BioModels Database and identified by: BIOMD0000000474 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Oxidative stress caused by exposure to reactive oxygen species (ROS), is a major challenge for aerobic and especially anaerobic organisms. Bacteria coordinate the response to oxidative stress through the LysR-type transcriptional regulator (LTTR) OxyR. Extensive studies have focused on the classical Escherichia coli system to shed light on the mode of action of defensive weapons against oxidative stress. The underlying mechanism is mediated via the formation of redox-dependent disulfide bond between two conserved cysteines of OxyR, thus activating transcription of members of the OxyR regulon. However, only fragmentary information on the regulation and function of OxyR has been gleaned through genetic and biochemical analyses in the important opportunistic pathogen P. aeruginosa. In this report, we used a comprehensive transcriptional profiling analysis to delineate the OxyR regulon under three conditions (KingM-bM-^@M-^Ys A medium [Pseudomonas medium or PM], Luria Broth (LB), and LB when oxyR is overexpressed), to investigate its roles in different cellular aspects that are independent of the classical oxidative stress response. Interestingly, when grown in LB, OxyR was found to regulating many genes involved in the process of inter-cellular communication known as quorum sensing (QS). In contrast, when grown in PM, OxyR regulate the expression of a newly identified CSS (cell-surface signaling) system in an OxyR-dependent fashion. In addition, the results from oxyR overexpression further confirmed that OxyR was linked to regulation of QS and Type 3 Secretion (T3SS) in addition to the regulation of antioxidative genes. Taken together, our results show that, apart from its dominant role in defense against oxidative stress in P. aeruginosa, OxyR acts as a global regulator that provides a link between the regulation of oxidative stress response, QS and virulence. 15 samples, representing 5 different biological conditions, including 3 biological replicates for each condition

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Contributions of transcription and mRNA turnover to gene expression dynamics of fission Yeast Extract mediumast in response to oxidative stress

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