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

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

PROVIDER: PRJNA1109775 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28980150_1.fastq.gz	Fastqsanger.gz
	SRR28980150_2.fastq.gz	Fastqsanger.gz
	SRR28980151_1.fastq.gz	Fastqsanger.gz
	SRR28980151_2.fastq.gz	Fastqsanger.gz
	SRR28980152_1.fastq.gz	Fastqsanger.gz

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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

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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]

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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]

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

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

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Integrator loss leads to dsRNA formation that triggers the Integrated Stress Response

Project description:Integrator (INT) is a metazoan-specific complex that targets promoter-proximally paused RNA polymerase II (RNAPII) for termination, preventing immature RNAPII from entering gene bodies and functionally attenuating transcription of stress-responsive genes. Mutations in INT subunits are associated with many human diseases, including cancer, ciliopathies and neurodevelopmental disorders, but how reduced INT activity contributes to disease is unknown. Here, we demonstrate that loss of INT-mediated termination in human cells triggers the integrated stress response (ISR). INT-depletion causes upregulation of short genes such as the ISR transcription factor ATF3. Further, immature RNAPII that escapes into genes upon INT-depletion is prone to premature termination, generating incomplete pre-mRNAs with retained introns. Retroelements within retained introns form double-stranded RNA (dsRNA) that is recognized by Protein Kinase R (PKR), which drives ATF4 activation and prolonged ISR. Critically, patient cells with INT mutations exhibit dsRNA accumulation and ISR activation, thereby implicating chronic ISR in diseases caused by INT-deficiency.

2026-01-08 | PXD060648 | Pride

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-16 | GSE267239 | GEO

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

Project description:Acute loss of INT induces transcription factors that initiate stress-responses like the Integrated Stress Response (ISR). Inefficient elongation upon INT loss enables termination in introns and dsRNA formation. dsRNA is recognized by PKR, which persistently activates the ISR in samples from patients with INT mutations

2025-04-16 | GSE283862 | GEO

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

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

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