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Plasticity of the Mammalian Integrated Stress Response [eIF2B5]

ABSTRACT: Plasticity of the Mammalian Integrated Stress Response [eIF2B5]

PROVIDER: PRJNA1114733 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29130907_1.fastq.gz	Fastqsanger.gz
	SRR29130907_2.fastq.gz	Fastqsanger.gz
	SRR29130908_1.fastq.gz	Fastqsanger.gz
	SRR29130908_2.fastq.gz	Fastqsanger.gz
	SRR29130909_1.fastq.gz	Fastqsanger.gz

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Plasticity of the Mammalian Integrated Stress Response [eIF2B5]

Project description:Decreased nucleotide exchange activity of the eukaryotic translation initiation factor eIF2B coupled with increased phosphorylation of eIF2alpha (eIF2alpha-p) is a hallmark of the “canonical” integrated stress response (c-ISR). In mammals, however, it is unclear whether decreased eIF2B activity in absence of alterations in eIF2alpha-p which occurs in human disease including leukodystrophies, is synonymous to c-ISR. Herein, we describe a previously unknown mechanism of adaptation to decreased eIF2B activity, distinct from c-ISR, which we term “split” ISR (s-ISR). We demonstrate that s-ISR comprises translation reprogramming of only a subset of c-ISR mRNA targets which is accompanied by distinct transcriptomes. In contrast to c-ISR, s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (e.g., PCK2), resulting in metabolic adaptations to maintain cellular bioenergetics under conditions of low eIF2B activity. Overall, these data demonstrate hitherto-unappreciated plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of increased eIF2-p, activates an eIF4E/ATF4/PCK2 axis to maintain energy homeostasis.

2025-01-22 | GSE268130 | GEO

Plasticity of the Mammalian Integrated Stress Response [eIF2B5_eIF4E]

Project description:Plasticity of the Mammalian Integrated Stress Response [eIF2B5_eIF4E]

| PRJNA1114731 | ENA

Plasticity of the Mammalian Integrated Stress Response [atf4]

Project description:Plasticity of the Mammalian Integrated Stress Response [atf4]

| PRJNA1114729 | ENA

Plasticity of the Mammalian Integrated Stress Response [eIF2B5_eIF4E]

2025-01-22 | GSE268132 | GEO

Plasticity of the Mammalian Integrated Stress Response [atf4]

2025-01-22 | GSE268127 | GEO

OMA1, DELE1 and HRI relay mitochondrial stress to the mammalian integrated stress response

Project description:OMA1, DELE1 and HRI relay mitochondrial stress to the mammalian integrated stress response

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Epidermal basal cell-specific in vivo ribosome profiling to describe the translation landscape of HrasG12V and Eif2b5

Project description:eIF2B5 is necessary for HrasG12V hyperplastic growth. Ribosome profiling was used to describe HrasG12V and WT dependence on eIF2B5-mediated translation.

2020-06-10 | GSE126660 | GEO

STAMPScreen: An Integrated Pipeline for Mammalian Genetic Screening

Project description:STAMPScreen: An Integrated Pipeline for Mammalian Genetic Screening

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Transcriptional characterization of the Eif2b5[R191H] loss-of-function mouse model

Project description:The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. We have characterized an eIF2B loss of function (LOF) mouse model, carrying the homozygous Eif2b5[R191H] mutation that is homologous to the Vanishing White Matter Disease (VWMD)-causing human R195H variant. Characterization of previously reported transcript markers in animals 3-4 weeks of age confirmed ISR activation in the brain, but not in heterozygous or wild-type littermates.The robust elevation of ISR markers was further confirmed in bulk brain RNA sequencing analysis of a separate cohort of homozygous mutants and wild-type littermates. Known ATF4 targets feature prominently among the most strongly up-regulated genes in the eIF2B mutant compared to WT littermates.

2023-08-22 | GSE240150 | GEO

Integrated stress response

Project description:Comparison of genes induced during activation of the Integrated Stress Response by tunicamycin or following AP20187 induced dimerization of a Fv2E-PERK chimera in wildtype cells and cells carrying mutations in key ISR signaling molecules. Keywords: other

2003-10-07 | GSE700 | GEO

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