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Double-stranded RNA triggers a distinct integrated stress response in the early embryo

ABSTRACT: Double-stranded RNA triggers a distinct integrated stress response in the early embryo

PROVIDER: PRJNA980581 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24835337_1.fastq.gz	Fastqsanger.gz
	SRR24835337_2.fastq.gz	Fastqsanger.gz
	SRR24835338_1.fastq.gz	Fastqsanger.gz
	SRR24835338_2.fastq.gz	Fastqsanger.gz
	SRR24835339_1.fastq.gz	Fastqsanger.gz

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Double-stranded RNA triggers a distinct integrated stress response in the early embryo [cas9 tol2]

Project description:Double-stranded RNA triggers a distinct integrated stress response in the early embryo [cas9 tol2]

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Double-stranded RNA triggers a distinct integrated stress response in the early embryo [dsRNA tp53]

Project description:Double-stranded RNA triggers a distinct integrated stress response in the early embryo [dsRNA tp53]

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Double-stranded RNA triggers a distinct integrated stress response in the early embryo [RNA-seq, Ribo-seq]

Project description:Double-stranded RNA triggers a distinct integrated stress response in the early embryo [RNA-seq, Ribo-seq]

| PRJNA1104180 | ENA

Double-stranded RNA triggers a distinct integrated stress response in the early embryo [RNA-seq, Ribo-seq]

Project description:Double-stranded RNA (dsRNA) is associated with virus infections and is present as by-products during the transcription of synthetic mRNA, which has been widely used in gene gain-of-function studies and serves as a core component in emerging mRNA-based therapies1-4. The presence of dsRNA in host cells induces an integrated stress response that functions to prevent virus replication and infection5,6. Unlike differentiated cells, undifferentiated cells adopt a distinct defense strategy against RNA virus infection7, but the mechanism is unclear. We show a previously unidentified response triggered by dsRNA in the early embryo. Although dsRNA causes a global protein translation inhibition in a PKR-eIF2α independent manner and leads to developmental delay and cell necrosis, it also strongly induces p53 activation, which then upregulates Interferon Stimulated Genes independently of interferon ligands. Importantly, we demonstrate that the burst of p53 signaling dose not result in cell death but functions as a protective mechanism against deleterious translation blockage by slowing down global protein degradation via ISGylation. Our work has identified a distinct dsRNA-induced stress response in the embryo, reflecting an ancient innate immune memory before the establishment of the IFN system. It also raises the provocative question as to the original protective role of p53 during evolution.

2024-04-26 | GSE265771 | GEO

Double-stranded RNA triggers a distinct integrated stress response in the early embryo [dsRNA tp53]

Project description:Gene functional study and the emerging mRNA therapy technology heavily rely on in vitro transcribed (IVT) mRNA, but the double-stranded RNA (dsRNA) by-product generated during IVT is often recognized by cells as a marker of virus replication, leading to the integrated stress response (ISR).The biological effects of dsRNA in undifferentiated cells differ significantly from those of differentiated counterparts.Here, we found that dsRNA triggered an unprecedented ISR in zebrafish early embryos, leading to developmental delay, severe cell necrosis, and lethal malformations.Mechanistically, dsRNA stimulation caused a PKR-eIF2α independent global translation inhibition and a burst of p53 signaling. In turn, p53 activated Interferon Stimulated Genes (ISGs) and other defense-related genes in the absence of the IFN system. Unexpectedly, p53 does not promote cell death; instead, it plays a protective role in weakening the damage of translation repression by compromising protein turnover via enhanced ISGylation.This study thus unveils a distinct ISR upon dsRNA stimulation, which may help perform faithful gene overexpression in early embryos and shed light on the strategies of undifferentiated cells against RNA virus infection.

2024-01-01 | GSE234229 | GEO

Double-stranded RNA triggers a distinct integrated stress response in the early embryo [cas9 tol2]

2024-01-01 | GSE234227 | GEO

Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA

Project description:Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA

| PRJNA1110594 | ENA

Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [PROseq]

Project description:Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [PROseq]

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Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [RIPseq]

Project description:Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [RIPseq]

| PRJNA1109399 | ENA

Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [48h_INTS8_RNAseq]

Project description:Disruption of the Integrator complex triggers the Integrated Stress Response through formation of double-stranded RNA [48h_INTS8_RNAseq]

| PRJNA1195926 | ENA

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