ArticleGenes & development2014
PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94 citing papers in PubMed, 139 citations in OpenAlex.
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- Regulation of mRNA decay and translation during the mammalian cell cycle.RNA (New York, N.Y.) · 2026Review
- The nuclear cap-binding complex safeguards stress-resistant protein synthesis and proliferation of stem cells.Science advances · 2026Article
- Defects in intron recycling suppress the antiviral response via a mechanism of intronic endogenous dsRNA.The Journal of experimental medicine · 2026Article
- RNA binding protein Musashi1 interacts with the viral genomic RNA and restricts SARS-CoV-2 infection by repressing translation.Nucleic acids research · 2026Article
- Decreased tRNA abundance contributes to decreased translation elongation rate in a prolonged mitosis.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic Analysis of the Antiviral Responses in Ovine Type II Alveolar Epithelial Cells During Early Stage of Bluetongue Virus Infection.Animals : an open access journal from MDPI · 2026Article
- Analysis of Endogenously Expressed Double-Stranded RNAs in Human Cultured Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.PLoS pathogens · 2025Article
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- 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
- Self-modulating therapeutic platform using engineered miRNA-responsive oligonucleotides.Nano convergence · 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
- Cellular dsRNA interactome captured by K1 antibody reveals the regulatory map of exogenous RNA sensing.Communications biology · 2025Article
- Induction of translation-suppressive G3BP1hLife · 2025Article
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34 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the α subunit of eukaryotic initiation factor 2 (eIF2α). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as cyclins A and B and Polo-like kinase 1 and phosphorylation of histone H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells.
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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.