ArticleJournal of molecular biology2008
Mechanism of PKR Activation by dsRNA.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 209 citations in OpenAlex.
- The pathogenicity and virulence of Sindbis virus.Virulence · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- PKR engages viral RNA and intron-retained host transcripts during poxvirus infection.Cell reports · 2026Article
- A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells.Nature biotechnology · 2026Article
- DHX36 is a regulatory switch in the interferon-mediated antiviral response.Science advances · 2026Article
- Uridine analogs prevent stress granule formation, not by blocking PKR recognition, but by inhibiting the synthesis of T7 RNA polymerase byproducts.RNA (New York, N.Y.) · 2026Article
- Defects in intron recycling suppress the antiviral response via a mechanism of intronic endogenous dsRNA.The Journal of experimental medicine · 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
- Transgenic approaches in the pathogenic free-living amoebae: what are the hurdles?Parasitology · 2026Review
- Template nicking suppresses promoter-independent antisense transcription in IVT via R-loop-mediated strand displacement.Nucleic acids research · 2026Article
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- PUS1 Drives Renal Cancer Progression by Preventing Formation of Endogenous Double-stranded RNAs.International journal of biological sciences · 2026Article
- ADAR1: a central regulator of dsRNA sensing in host-virus interactions.Frontiers in immunology · 2026Review
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.PLoS pathogens · 2025Article
- Single-Cell Transcriptome Patterns of Transposable Elements in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Transcription, Maturation and Degradation of Mitochondrial RNA: Implications for Innate Immune Response.Biomolecules · 2025Review
- Enhancing thiazolide efficacy: C-4 aryl modifications drive selective SARS-CoV-2 inhibition.Future medicinal chemistry · 2025Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase R (PKR) is a central component of the interferon antiviral defense pathway. Upon binding double-stranded RNA (dsRNA), PKR undergoes autophosphorylation reactions that activate the kinase. PKR then phosphorylates eukaryotic initiation factor 2alpha, thus inhibiting protein synthesis in virally infected cells. Using a series of dsRNAs of increasing length, we define the mechanism of PKR activation. A minimal dsRNA of 30 bp is required to bind two PKR monomers and 30 bp is the smallest dsRNA that elicits autophosphorylation activity. Thus, the ability of dsRNAs to function as PKR activators is correlated with binding of two or more PKR monomers. Sedimentation velocity data fit a model where PKR monomers sequentially attach to a single dsRNA. These results support an activation mechanism where the role of the dsRNA is to bring two or more PKR monomers in close proximity to enhance dimerization via the kinase domain. This model explains the inhibition observed at high dsRNA concentrations and the strong dependence of maximum activation on dsRNA binding affinity. Binding affinities increase dramatically upon reducing the salt concentration from 200 to 75 mM NaCl and we observe that a second PKR can bind to the 20-bp dsRNA. Nonspecific assembly of PKR on dsRNA occurs stochastically without apparent cooperativity.
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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.