Exposure of cells to suboptimal growth conditions or to any environment that reduces cell viability or fitness can be considered a stress.
Adaptive responses to stress depend on the organism and are comprised of both generic responses shared by many stresses and specific responses dedicated to particular stresses.
Eukaryotic cells have evolved sophisticated sensing mechanisms and signal transduction systems that can produce accurate dynamic outcomes in response to stresses.
Adaptation to stress involves an extensive reorganization of the gene expression programme.
Control of gene expression following exposure to stress is tightly regulated and reversible. This control is achieved by different molecular mechanisms that are highly dependent on the particular stress and organism.
The pattern of gene expression that is observed in response to stress is achieved by fine regulation of multiple steps of the mRNA biogenesis and mRNA fate.
Nucleosome remodelling is important in stress-induced gene expression and might be important in providing transcriptional activators and general transcription machinery with full access to stress-responsive genes.
RNA polymerase II pausing is a mechanism that enables rapid gene induction, and it is used in several organisms to coordinate gene expression.
Signalling kinases are an integral part of transcription platforms.
Acute stress puts cells at risk, and rapid adaptation is crucial for maximizing cell survival. Cellular adaptation mechanisms include modification of certain aspects of cell physiology, such as the induction of efficient changes in the gene expression programmes by intracellular signalling networks. Recent studies using genome-wide approaches as well as single-cell transcription measurements, in combination with classical genetics, have shown that rapid and specific activation of gene expression can be accomplished by several different strategies. This article discusses how organisms can achieve generic and specific responses to different stresses by regulating gene expression at multiple stages of mRNA biogenesis from chromatin structure to transcription, mRNA stability and translation.
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The laboratory of F.P. and E.d.N. is supported by grants from the Ministerio de Ciéncia y Innovación, the Consolider Ingenio 2010 programme and FP7 UNICELLSYS grant to F.P., E.d.N. and G.A. F.P. is also supported by the Fundación Marcelino Botín (FMB) and ICREA Acadèmia (Generalitat de Catalunya). We apologize to colleagues in the field for not citing all relevant papers owing to space constraints.
The authors declare no competing financial interests.
Mucins are a family of high-molecular-mass glycoproteins characterized by a high content of Ser and Thr residues that are organized as heavily glycosylated tandem repeats. Mucins are the main components of mucus, an adhesive and viscoelastic gel covering the surface of internal epithelia.
- Thermosensory structures
Biomolecules that contain particular structures whose conformations are susceptible to temperature changes and behave as primary sensors of temperature. Examples of thermosensory structures include DNA, RNA, specific proteins or lipids from cellular membranes.
Proteins that assist in the correct folding or assembly of other proteins.
- Fluorescence recovery after photobleaching
(FRAP). An optical technique for quantifying the kinetics of diffusion or active movement of biological molecules. This method involves labelling a specific cell component with a fluorescent molecule, followed by photobleaching a sharply defined region of the cell. Imaging is used to observe the subsequent rates and patterns of fluorescence recovery.
A chromatin-remodelling complex that uses DNA-dependent ATP hydrolysis to mobilize nucleosomes and render the DNA accessible for various nuclear processes. The SWI/SNF complex is required for expression of many inducible genes.
- Chromatin immunoprecipitation
(ChIP). A method used to determine whether and where a given protein associates to DNA. This technique is also used to characterize the distribution of specific chromatin marks on the genome.
A ~30-subunit co-activator complex that is necessary for successful transcription of class II promoters of metazoan genes. Mediator coordinates the signals between enhancers and the general transcription machinery through its interaction with RNA polymerase II and site-specific factors.
The yeast SAGA complex (Spt–Ada–Gcn5–acetyltransferase) is a large, multi-subunit complex containing several enzymatic activities that are linked to activators and histones and involved in core promoter selectivity. SAGA is necessary for turning on genes that respond to stress. It shows a high degree of structural conservation with a human complex: the TATA box binding protein (TBP)-free TAFII-containing complex.
An oncogene that is activated by diverse stimuli and stresses, including serum growth factors and MAPK cascades. Members of the FOS family can dimerize with JUN proteins to form the activator protein 1 (AP1) transcription factor, which has been involved as a regulator of cell proliferation, differentiation and transformation.
The post-translational modification of proteins that involves the covalent attachment of a small ubiquitin-like modifier (SUMO) and regulates the interactions of those proteins with other macromolecules.
- AU-rich elements
(AREs). Regulatory elements usually located in the 3′UTR of mRNAs that mediate recognition of an array of RNA-binding proteins and are determinant of RNA stability and translation.
- Stress granules
Cytoplasmic RNA–protein complexes containing non-translating mRNAs, translation initiation components and other additional proteins that affect mRNA function. Stress granules are induced by stress and affect mRNA translation and stability.
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de Nadal, E., Ammerer, G. & Posas, F. Controlling gene expression in response to stress. Nat Rev Genet 12, 833–845 (2011). https://doi.org/10.1038/nrg3055
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