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Hepatic transcriptome of eIF2α heterozygotic mouse

ABSTRACT: Hepatic transcriptome of eIF2α heterozygotic mouse

PROVIDER: PRJNA609634 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11213532_1.fastq.gz	Fastqsanger.gz
	SRR11213532_2.fastq.gz	Fastqsanger.gz
	SRR11213533_1.fastq.gz	Fastqsanger.gz
	SRR11213533_2.fastq.gz	Fastqsanger.gz
	SRR11213534_1.fastq.gz	Fastqsanger.gz

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Hepatic transcriptome of eIF2α heterozygotic mouse

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Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells [RNA-Seq]

Project description:The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2αbecomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESC) is largely unexplored. We employ a multi-omics approachconsisting of ribosome profiling, proteomics, and metabolomics inwild-type(eIF2α+/+)andphosphorylation-deficient mutant eIF2α(eIF2αA/A)mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naïve pluripotency. We show a transient increase in p-eIF2α in the naïve epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins which govern pluripotency, chromatin organization, and glutathione synthesis.Thus, p-eIF2αacts as a key regulator of the naïve pluripotency gene regulatory network.

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Hepatic transcriptome of wildtype and Cugbp1 knockout mouse neonates.

Project description:We characterize the hepatic transcriptome of wildtype and Cugpb1 knockout mice at day 3 of life using the Agilent Whole Mouse Genome Oligo Microarray, focusing on the role of Cugbp1 in the differentiation of hepatic stem cells into hepatocytes.

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The Small Molecule ISRIB Reverses the Effects of eIF2α Phosphorylation on Translation and Stress Granule Assembly

Project description:We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation and cognitive loss. Ribosome profiling with paired RNA-seq

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