Global Gene Expression Profiling Reveals Widespread yet Distinctive Translational Responses to Different Eukaryotic Translation Initiation Factor 2B-Targeting Stress Pathways
Julia B. Smirnova,Julian N. Selley,Fátima Sánchez-Cabo,Kathleen M. Carroll,A A Eddy,John E.G. McCarthy,Simon J. Hubbard,Graham D. Pavitt,Chris M. Grant,Mark P. Ashe +9 more
TLDR
Yeast mRNAs are identified that are translationally maintained following either amino acid depletion or fusel alcohol addition, which demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress.Abstract:
Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.read more
Citations
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Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
TL;DR: A ribosomesome-profiling strategy based on the deep sequencing of ribosome-protected mRNA fragments is presented and enables genome-wide investigation of translation with subcodon resolution and is used to monitor translation in budding yeast under both rich and starvation conditions.
Journal ArticleDOI
Translational Regulation of Gene Expression during Conditions of Cell Stress
TL;DR: A number of stresses, including nutrient stress, temperature shock, DNA damage, and hypoxia, can lead to changes in gene expression patterns caused by a general shutdown and reprogramming of protein synthesis.
Journal ArticleDOI
The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae
TL;DR: The progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress is reviewed.
Journal ArticleDOI
Global Translational Responses to Oxidative Stress Impact upon Multiple Levels of Protein Synthesis
Daniel Shenton,Julia B. Smirnova,Julian N. Selley,Kathleen M. Carroll,Simon J. Hubbard,Graham D. Pavitt,Mark P. Ashe,Chris M. Grant +7 more
TL;DR: In this paper, the authors analyzed the regulation of protein synthesis in response to oxidative stress induced by exposure to H2O2 in the yeast Saccharomyces cerevisiae.
Journal ArticleDOI
The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels.
Pascale Daran-Lapujade,Sergio Rossell,Walter M. van Gulik,Marijke A. H. Luttik,Marco J. L. de Groot,Monique Slijper,Albert J. R. Heck,Jean-Marc Daran,Johannes H. de Winde,Hans V. Westerhoff,Jack T. Pronk,Barbara M. Bakker +11 more
TL;DR: A method is developed to dissect the hierarchical regulation of fluxes into contributions by transcription, translation, protein degradation, and posttranslational modification and it is found that transcription played a minor role, whereas regulation of protein synthesis or degradation was the most important.
References
More filters
Journal ArticleDOI
Bioconductor: open software development for computational biology and bioinformatics
Robert Gentleman,Vincent J. Carey,Douglas M. Bates,Benjamin M. Bolstad,Marcel Dettling,Sandrine Dudoit,Byron Ellis,Laurent Gautier,Yongchao Ge,Jeff Gentry,Kurt Hornik,Torsten Hothorn,Wolfgang Huber,Stefano Maria Iacus,Rafael A. Irizarry,Friedrich Leisch,Cheng Li,Martin Maechler,A. J. Rossini,Günther Sawitzki,Colin A. Smith,Gordon K. Smyth,Luke Tierney,Jean Yang,Jianhua Zhang +24 more
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Journal ArticleDOI
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Rafael A. Irizarry,Bridget G. Hobbs,Francois Collin,Yasmin Beazer-Barclay,Kristen J. Antonellis,Uwe Scherf,Terence P. Speed +6 more
TL;DR: There is no obvious downside to using RMA and attaching a standard error (SE) to this quantity using a linear model which removes probe-specific affinities, and the exploratory data analyses of the probe level data motivate a new summary measure that is a robust multi-array average (RMA) of background-adjusted, normalized, and log-transformed PM values.
Journal ArticleDOI
A comparison of normalization methods for high density oligonucleotide array data based on variance and bias
TL;DR: Three methods of performing normalization at the probe intensity level are presented: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure and the simplest and quickest complete data method is found to perform favorably.
Journal ArticleDOI
Summaries of Affymetrix GeneChip probe level data
Rafael A. Irizarry,Benjamin M. Bolstad,Francois Collin,Leslie Cope,Bridget G. Hobbs,Terence P. Speed,Terence P. Speed +6 more
TL;DR: It is found that the performance of the current version of the default expression measure provided by Affymetrix Microarray Suite can be significantly improved by the use of probe level summaries derived from empirically motivated statistical models.
Journal ArticleDOI
Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.
Alvis Brazma,Pascal Hingamp,John Quackenbush,Gavin Sherlock,Paul T. Spellman,Chris Stoeckert,John Aach,Wilhelm Ansorge,Catherine A. Ball,Helen C. Causton,Terry Gaasterland,Patrick Glenisson,Frank C. P. Holstege,Irene F. Kim,Victor Markowitz,John C. Matese,Helen Parkinson,Alan J. Robinson,Ugis Sarkans,Steffen Schulze-Kremer,Jason E. Stewart,Ronald C. Taylor,Jaak Vilo,Martin Vingron +23 more
TL;DR: The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools.