ArticleCell2025
Integrator loss leads to dsRNA formation that triggers the integrated stress response.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed.
- Targeting the Chromatin-Modifying Enzyme, KDM5C, Enhances AKT Inhibition Response in ER+ Breast Cancer.Molecular cancer therapeutics · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- Assembly of exon junction complexes on spliceosomes begins before spliceosome activation.Nucleic acids research · 2026Article
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Single-Cell Profiling Reveals a Protective WNT5A-ATF3-FOSB Signaling Axis in Hair Follicle Stem Cells During Androgenetic Alopecia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PKR engages viral RNA and intron-retained host transcripts during poxvirus infection.Cell reports · 2026Article
- Caspase-3 regulates RNA splicing and mitochondrial dynamics in microglia during Parkinson's disease.Cell death & disease · 2026Article
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Leucyl tRNA synthetase ameliorates cholestatic liver injury by inhibiting integrated stress response in mice.Scientific reports · 2026Article
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- Light-Dependent Temporal Reprogramming of Alternative Splicing Dynamics Under Salt Stress in Sweet Potato (Plants (Basel, Switzerland) · 2026Article
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Adulthood depletion of Integrator extends lifespan and healthspan via defective pre-mRNA processing.bioRxiv : the preprint server for biology · 2026Article
- Structural and mechanistic basis of ADAR1-mediated RNA editing and immune regulation.Cell insight · 2026Review
- CPF-CF-terminated snoRNAs shuttle through the cytoplasm via an mRNA guard protein-mediated surveillance mechanism.Nature communications · 2026Article
- Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to Pumilio-mediated decay.Nucleic acids research · 2026Article
- PUS1 Drives Renal Cancer Progression by Preventing Formation of Endogenous Double-stranded RNAs.International journal of biological sciences · 2026Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
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 the 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 activating transcription factor 3 (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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.