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Regulation of translation elongation and integrated stress response in heat-shocked neurons

ABSTRACT: Regulation of translation elongation and integrated stress response in heat-shocked neurons

PROVIDER: PRJNA995794 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25309362.fastq.gz	Fastqsanger.gz
	SRR25309363.fastq.gz	Fastqsanger.gz
	SRR25309364.fastq.gz	Fastqsanger.gz
	SRR25309365.fastq.gz	Fastqsanger.gz
	SRR25309366.fastq.gz	Fastqsanger.gz

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Regulation of translation elongation and integrated stress response in heat-shocked neurons

Project description:Neurons in the mammalian central nervous system adapt to changes in temperature through molecular mechanisms that are poorly understood. Here, in response to elevated temperatures, we show that primary mouse neurons isolated from the cortex experience a global downregulation of polysome-dependent translation and a concomitant activation of a unique transcriptional program. These new transcripts were found associated with ribosomes during initial stages of this heat-induced stress response, during which time there was little global protein production. Returning neurons to baseline temperature within a defined window of time (<60 minutes) was necessary for translation to return to control levels and ultimately for neuronal survival. Neurons placed at baseline temperature beyond this time window did not recover translation and died. Among the many transcripts upregulated during heat stress, we observed a ~350-fold increase in Hspa1a and yet no detectable translation of Hsp70 protein until recovery at baseline temperature. We considered that this heat stress response was relevant to neuronal resilience and survival following recovery. To begin to test this idea, we chose to use orthogonal approaches to suppress Hsp70 expression or function. We found, in neurons which had experienced heat stress, that Hsp70 was critical for preventing activation of cell death pathways during recovery. Taken together, our findings suggest that neurons are unique in their response to heat stress in that during a finite window they poise ribosomes on new transcripts, such as Hspa1a, thus preparing for exclusive expression of these factors in the event that recovery is an option.

2025-04-22 | GSE237598 | GEO

Regulation of translation elongation and integrated stress response in heat-shocked neurons.

Project description: Not available

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Permanganate ChIP-seq analysis of Pol II in nonheat shocked and heat shocked Drosophila S2R+ cells and nonheat shocked BG3 cells

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Measuring the dependence of the yeast heat shock response on intracellular pH and translation during stress

Project description:S. cerevisiae cells acidify when they experience stressful temperatures. In addition, newly-translated proteins are thought to misfold, triggering the heat shock response. To determine whether heat-shock associated acidification and translation state are important for the cellular response, we manipulated intracellular pH, blocked translation, heat shocked cells, and sequenced the transcriptome.

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An Integrated Approach Reveals Regulatory Controls on Bacterial Translation Elongation

Project description:An Integrated Approach Reveals Regulatory Controls on Bacterial Translation Elongation

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An Integrated Approach Reveals Regulatory Controls on Bacterial Translation Elongation

Project description:Ribosomes elongate at a nonuniform rate during translation. Theoretical models and experiments disagree on the in vivo determinants of elongation rate and the mechanism by which elongation rate affects protein levels. To resolve this conflict, we measured transcriptome-wide ribosome occupancy under multiple conditions and used it to formulate a whole-cell model of translation in E. coli. Our model predicts that elongation rates at most codons during nutrient-rich growth are not limited by the intracellular concentrations of aminoacyl-tRNAs. However, elongation pausing during starvation for single amino acids is highly sensitive to the kinetics of tRNA aminoacylation. We further show that translation abortion upon pausing accounts for the observed ribosome occupancy along mRNAs during starvation. Abortion reduces global protein synthesis, but it enhances the translation of a subset of mRNAs. These results suggest a regulatory role for aminoacylation and abortion during stress, and our study provides an experimentally constrained framework for modeling translation.

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Permanganate ChIP-seq analysis of Pol II in nonheat shocked and heat shocked Drosophila S2R+ cells and nonheat shocked BG3 cells

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