ArticleNature communications2025
PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Mitochondrial RNA-Type I Interferon Axis in Sjögren's Disease: Molecular Mechanisms and Translational Implications.International journal of molecular sciences · 2026Review
- PKR engages viral RNA and intron-retained host transcripts during poxvirus infection.Cell reports · 2026Article
- Review
- CAV2 Modulates Cetuximab Sensitivity in HNSCC via Ubiquitin-Mediated Disruption of the PACT-PKR Axis.Cancers · 2026Article
- Structural and mechanistic basis of ADAR1-mediated RNA editing and immune regulation.Cell insight · 2026Review
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Toward unraveling molecular grammars for dsRNA-binding proteins: substrate recognition to binding mechanisms.BMB reports · 2025Review
- Article
- PACT suppresses PKR activation through dsRNA binding and dimerization, and is a therapeutic target for triple-negative breast cancer.RNA (New York, N.Y.) · 2025Article
- From activator to suppressor: PACT is joining the company of PKR negative regulators.RNA (New York, N.Y.) · 2025Article
- RNA triggers chronic stress during neuronal aging.bioRxiv : the preprint server for biology · 2025Article
- TRBP modulates RLR signaling by inhibiting PKR-mediated antiviral stress granule formation.Scientific reports · 2025Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
- PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration.Nature communications · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The innate immune sensor PKR for double-stranded RNA (dsRNA) is critical for antiviral defense, but its aberrant activation by cellular dsRNA is linked to various diseases. The dsRNA-binding protein PACT plays a critical yet controversial role in this pathway. We show that PACT directly suppresses PKR activation by endogenous dsRNA ligands, such as inverted-repeat Alu RNAs, which robustly activate PKR in the absence of PACT. Instead of competing for dsRNA binding, PACT prevents PKR from scanning along dsRNA-a necessary step for PKR molecules to encounter and phosphorylate each other for activation. While PKR favors longer dsRNA for increased co-occupancy and scanning-mediated activation, longer dsRNA is also more susceptible to PACT-mediated regulation due to increased PACT-PKR co-occupancy. Unlike viral inhibitors that constitutively suppress PKR, this RNA-dependent mechanism allows PACT to fine-tune PKR activation based on dsRNA length and quantity, ensuring self-tolerance without sequestering most cellular dsRNA.
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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.