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Article

Integrator loss leads to dsRNA formation that triggers the integrated stress response.

Cell - 12 Jun 2025

Baluapuri Apoorva, Zhao Nicole ChenCheng, Marina Ryan J, Huang Kai-Lieh, Kuzkina Anastasia, Amodeo Maria E, Stein Chad B, Ahn Lucie Y, Farr Jordan S, Schaffer Ashleigh E, Khurana Vikram, Wagner Eric J, Adelman Karen

Abstract excerpt

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...

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Share to Activating Transcription Factor 4
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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Source

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Identifiers

PMID: 40233738
DOI: 10.1016/j.cell.2025.03.025
PMCID: PMC12167153

Genes

ATF3
ATF4

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

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The Integrator complex prevents premature neuronal differentiation through global control of transcription elongationSemantic proximity Read ↗

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Termination dynamics set RNAPII elongation rate and gate the response to CDK12 inactivationSemantic proximity Read ↗

Transcription directionality is licensed by Integrator at active human promotersSemantic proximity Read ↗

SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape.Semantic proximity Read ↗

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