Long non-coding Satellite III RNAs link the heat shock response and cell proliferation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58439 | GEO | 2015/12/31
SECONDARY ACCESSION(S): PRJNA252616
REPOSITORIES: GEO
Similar Datasets
Project description:Genomes of complex organisms encode a wide variety of long non-coding RNAs (lncRNAs) that regulate gene expression. In human cells exposed to heat stress, transcription of lncRNAs is highly induced from Satellite III sequences located primarily within locus 9q12. Expression of Sat III transcripts is dependent on heat shock factor 1, the master regulator of the heat shock response. Sat III transcripts serve as the backbone of specific subnuclear structures called nuclear Stress Bodies, nSBs. Despite being known for two decades, the function of nSBs and Sat III transcripts is unknown, which prompted us to conduct RNA profiling in human cells where Sat III transcripts were either intact or downregulated. Comparison of these cells revealed that under stress conditions, Sat III transcripts are involved in regulating a plethora of genes, including such associated with cell growth and protein homeostasis. Our results show that the presence of Sat III transcripts has a repressive effect on cell proliferation. We propose a model in which the inducible expression of Sat III transcripts restrains cell proliferation, allowing the cell to assess whether to grow or undergo apoptosis, and thereby suggesting a function for these lncRNAs in cell fate decisions and in restoring protein homeostasis. Total RNA from HEK293T cells transfected with siRNA against Satellite III transcripts or scrambled siRNA and heat shocked 1 h at 42°C , or heat shocked 1 h at 42 °C followed by recovery for 6 h, or left untreated was compared.
2015-12-31 | E-GEOD-58439 | biostudies-arrayexpress
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors.
2016-09-07 | GSE73471 | GEO
Project description:During heat stress cyto-protective genes including heat shock proteins are transcriptionally up-regulated and post-transcriptional splicing is inhibited. In contrast, co-transcriptional mRNA-splicing is maintained. These factors closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response. Furthermore, there is evidence for BRD4's role in splicing regulation; Using RNA-Seq analyses we indeed found a significant increase in splicing inhibition, in particular intron retentions, during heat treatment in BRD4-deficient cells, but not under normal conditions. Subsequent experiments revealed that heat stress leads to the recruitment of BRD4 to nuclear stress bodies, to the interaction with the heat shock factor 1 (HSF1) and to the transcriptional up-regulation of non-coding Sat III RNA transcripts. These findings implicate BRD4 as a central regulator of splicing during heat stress. Since BRD4 is a potent target for anti-cancer therapies, our data linking BRD4 to the splicing machinery and the heat stress response - give additional insight into the mode of action of BRD4 inhibitors. WI38 cells have been treated by heatshock and anti BRD4 siRNA and combination.
2016-09-07 | E-GEOD-73471 | biostudies-arrayexpress
Project description:Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response
(HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular
chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms,
having stress-induced activation and feedback regulations with multiple partners, the HSR is still
incompletely understood. In this context, we propose a minimal molecular model for the gene
regulatory network of the HSR that reproduces quantitatively different heat shock experiments both
on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics
laws, is kept with a low dimensionality without altering the biological interpretation of the model
dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of
the network. Moreover, by a steady states analysis of the network, three different temperature stress
regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal
adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes
are consequences of the titration mechanism. The simplicity of the present model is of interest in
order to study detailed modelling of cross regulation between the HSR and other major genetic
networks like the cell cycle or the circadian clock.
Sivéry, A., Courtade, E., Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Physical biology, 13(6), 066008.
2022-01-25 | MODEL2201210001 | BioModels
Project description:Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian CHO cells. Our results indicate that mild heat triggers a distinct, dose dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of sat-urated membrane lipid species, specific lysophosphatidylinositol and sphingolipid species sug-gests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time dependent manner. RNAseq experiments reveal that mild heat initiate endoplasmic reticulum stress-related signaling cascades resulting in lipid re-arrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein denaturing high temperatures the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlights the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions.
2022-05-18 | GSE199531 | GEO
Project description:By using a 44k chicken Agilent microarray, we systematically analyzed the chicken hypothalamus transcriptome response to thermal stress. Twelve hypothalamus samples were chosen from three groups (four samples per group) to be used in chicken genome microarray to examine differential gene expression.We compared the expression profiles between each pairs of the three groups using the microarray data. Totally, 2474 genes were found to be differentially expressed in the three comparisons with pM-oM-<M-^\0.05 and fold change (FC) higher than 1.5 and the genes were mainly involved in self-regulation and compensation required to maintain homeostasis, including heat shock protein family, enzyme and the hormone, neurotransmitter, cell-cell signaling, metabolism and cytokines. The transcripts of heat shock protein including Hsp 40 and Hsp 90 were significantly changed respond to thermal stress and genes involved in regulation of cell morphogenesis were significantly upregulated in heat stressed group with comparison to control and temperature recovery group. Additionally, the down-regulated genes in both heat stress and temperature recovery groups compared to control group were enriched in muscle organ development, striated muscle tissue development, cardiac muscle tissue development and muscle tissue development, which indicates that muscle development was inhibited during and in short-term after heat treatment. Most of genes dysregulated in heat stress group were found to be recovered in temperature recovery group, which confirmed their roles they could play in coping with heat stress. The present study provides a broader understanding of molecular mechanisms underlying the stress response in chicken and discovery of novel genes that are regulated in a thermal stress specific manner. Hypothalamus samples were collected from non-heat treated group (reared at 25C, used as control), 24h 34C treated group (heat stress treated group) and temperature recovery group (25C for 24h followed heat stress).
2012-10-01 | E-GEOD-37400 | biostudies-arrayexpress
Project description:Proctor2005 - Actions of chaperones and their
role in ageing
This model is described in the article:
Modelling the actions of
chaperones and their role in ageing.
Proctor CJ, Soti C, Boys RJ,
Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TB.
Mech. Ageing Dev. 2005 Jan; 126(1):
119-131
Abstract:
Many molecular chaperones are also known as heat shock
proteins because they are synthesised in increased amounts
after brief exposure of cells to elevated temperatures. They
have many cellular functions and are involved in the folding of
nascent proteins, the re-folding of denatured proteins, the
prevention of protein aggregation, and assisting the targeting
of proteins for degradation by the proteasome and lysosomes.
They also have a role in apoptosis and are involved in
modulating signals for immune and inflammatory responses.
Stress-induced transcription of heat shock proteins requires
the activation of heat shock factor (HSF). Under normal
conditions, HSF is bound to heat shock proteins resulting in
feedback repression. During stress, cellular proteins undergo
denaturation and sequester heat shock proteins bound to HSF,
which is then able to become transcriptionally active. The
induction of heat shock proteins is impaired with age and there
is also a decline in chaperone function. Aberrant/damaged
proteins accumulate with age and are implicated in several
important age-related conditions (e.g. Alzheimer's disease,
Parkinson's disease, and cataract). Therefore, the balance
between damaged proteins and available free chaperones may be
greatly disturbed during ageing. We have developed a
mathematical model to describe the heat shock system. The aim
of the model is two-fold: to explore the heat shock system and
its implications in ageing; and to demonstrate how to build a
model of a biological system using our simulation system
(biology of ageing e-science integration and simulation
(BASIS)).
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000091.
To cite BioModels Database, please use:
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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.
2007-02-26 | BIOMD0000000091 | BioModels
Project description:Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine deaminases (ADARs) on dsRNAs. Although a significant fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicated changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here we performed high-throughput RNA sequencing of wildtype and ADAR mutant C. elegans worms after heat shock, to analyze the effect of heat shock stress on the expression pattern of genes. We found that ADAR regulation following heat shock does not involve directly heat shock related genes. Our analysis also revealed that, lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes upon heat shock in ADAR mutant worms, while they are downregulated in ADAR mutant worms under permissive conditions. Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shade a new light on the dynamics of gene expression under heat shock in relation to ADAR function.
2018-12-12 | GSE122015 | GEO
Project description:The Heat Shock response (HSR) is a highly conserved transcriptional program induced by the exposure to a variety of environmental stressors. Following an insult, a small subset of genes, known as the Heat Shock genes, are rapidly induced by the Heat Shock Factors (HSFs) to maintain protein homeostasis and ensure cell survival. In this study, we demonstrate that the RNAPII interactor RPRD1B is required for proper transcription of heat shock induced genes and for survival to heat shock.
2022-09-08 | GSE197993 | GEO
Project description:The Heat Shock response (HSR) is a highly conserved transcriptional program induced by the exposure to a variety of environmental stressors. Following an insult, a small subset of genes, known as the Heat Shock genes, are rapidly induced by the Heat Shock Factors (HSFs) to maintain protein homeostasis and ensure cell survival. In this study, we demonstrate that the RNAPII interactor RPRD1B is required for proper transcription of heat shock induced genes and for survival to heat shock.
2022-09-08 | GSE197992 | GEO