ArticlemBio2015
Stress granules regulate double-stranded RNA-dependent protein kinase activation through a complex containing G3BP1 and Caprin1.
Article in mBio, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 153 citations in OpenAlex.
- Loss of O-GlcNAc transferase activity impairs the dynamic formation of protective stress granules in ischemic cardiomyocytes.The Biochemical journal · 2026Article
- Stress granules formed during infections with RNA viruses have significant virus-specific differences in generation and composition.PLoS biology · 2026Article
- Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants.PLoS pathogens · 2026Article
- The assembly of stress granules during foot-and-mouth disease virus infection is uncoupled from activation of cellular intrinsic antiviral signalling.PLoS pathogens · 2026Article
- PKR condensation at viral replication complexes initiates its activation.Cell reports · 2026Article
- Equine infectious anemia virus blocks interferon responses through Rev-mediated activation of the stress granule-PKR-eIF2α pathway.PLoS pathogens · 2026Article
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants.bioRxiv : the preprint server for biology · 2026Article
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Herbal medicines against avian infectious bronchitis virus: shared host-directed and multi-stage antiviral pathways.Frontiers in veterinary science · 2026Review
- Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.PLoS pathogens · 2025Article
- Lactylation of HMGB1 at K177 Drives Nuclear Export of TIAR to Promote Hypoxia-Induced Stress Granule Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aspergillus fumigatus dsRNA virus promotes fungal fitness and pathogenicity in the mammalian host.Nature microbiology · 2025Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
- Loss of age-associated increase in mbioRxiv : the preprint server for biology · 2025Article
- Induction of translation-suppressive G3BP1hLife · 2025Article
- Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.Signal transduction and targeted therapy · 2024Review
- Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.Nucleic acids research · 2024Article
- Myosin-5a facilitates stress granule formation by interacting with G3BP1.Cellular and molecular life sciences : CMLS · 2024Article
- Viral hijacking of hnRNPH1 unveils a G-quadruplex-driven mechanism of stress control.Cell host & microbe · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledStress granules (SGs) are dynamic cytoplasmic repositories containing translationally silenced mRNAs that assemble upon cellular stress. We recently reported that the SG nucleating protein G3BP1 promotes antiviral activity and is essential in double-stranded RNA-dependent protein kinase (PKR) recruitment to stress granules, thereby driving phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we delineate the mechanism for SG-dependent PKR activation. We show that G3BP1 and inactive PKR directly interact with each other, dependent on both the NTF2-like and PXXP domains of G3BP1. The G3BP1-interacting protein Caprin1 also directly interacts with PKR, regulates efficient PKR activation at the stress granule, and is also integral for the release of active PKR into the cytoplasm to engage in substrate recognition. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. Our data links stress responses and their resultant SGs with innate immune activation through PKR without a requirement for foreign double-stranded RNA (dsRNA) pattern recognition. IMPORTANCE: Our previous work indicates that stress granules have antiviral activity and mediate innate immunity through functions of G3BP1; however, the mechanistic details of these functions were not resolved. We show that much of the antiviral activity of stress granules is contingent on the function of PKR in a complex with G3BP1 and Caprin1. The PKR-G3BP1-Caprin1 complex undergoes dynamic transitioning within and outside stress granules to accomplish PKR activation and translational repression. This mechanism appears to function distinctly from canonical pattern recognition of double-stranded RNA by PKR. Therefore, this mechanism bridges the stress response with innate immunity, allowing the cell to respond to many cellular stressors and amplify the pathogen pattern recognition systems of innate immunity.
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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.