ArticleRNA (New York, N.Y.)2016
Activation of PKR by short stem-loop RNAs containing single-stranded arms.
Article in RNA (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- 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
- Insect-specific virus platforms for arbovirus vaccine development.Frontiers in immunology · 2025Review
- Molecular Mechanisms of Innate Immune Sensing of Exogenous RNAs.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Activation of PKR by a short-hairpin RNA.Scientific reports · 2024Article
- Activation of PKR by a short-hairpin RNA.bioRxiv : the preprint server for biology · 2024Article
- Involvement of Protein Kinase R in Double-Stranded RNA-Induced Proteasomal Degradation of Hypoxia Inducible Factor-1α.Inflammation · 2023Article
- NS5A domain I antagonises PKR to facilitate the assembly of infectious hepatitis C virus particles.PLoS pathogens · 2023Article
- RNA Modification in Inflammatory Bowel Diseases.Biomedicines · 2022Review
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- Mucosal immunity and tRNA, tRF, and tiRNA.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Review
- Probing RNA-Protein Interactions and RNA Compaction by Sedimentation Velocity Analytical Ultracentrifugation.Methods in molecular biology (Clifton, N.J.) · 2020Article
- PKR activation by noncanonical ligands: a 5'-triphosphate requirement versus antisense contamination.RNA (New York, N.Y.) · 2019Article
- The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators.RNA (New York, N.Y.) · 2019Review
- Interaction of PKR with single-stranded RNA.Scientific reports · 2017Article
- Human noncoding RNA 886 (nc886) adopts two structurally distinct conformers that are functionally opposing regulators of PKR.RNA (New York, N.Y.) · 2017Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase R (PKR) is a central component of the innate immunity antiviral pathway and is activated by dsRNA. PKR contains a C-terminal kinase domain and two tandem dsRNA binding domains. In the canonical activation model, binding of multiple PKR monomers to dsRNA enhances dimerization of the kinase domain, leading to enzymatic activation. A minimal dsRNA of 30 bp is required for activation. However, short (∼15 bp) stem-loop RNAs containing flanking single-stranded tails (ss-dsRNAs) are capable of activating PKR. Activation was reported to require a 5'-triphosphate. Here, we characterize the structural features of ss-dsRNAs that contribute to activation. We have designed a model ss-dsRNA containing 15-nt single-stranded tails and a 15-bp stem and made systematic truncations of the tail and stem regions. Autophosphorylation assays and analytical ultracentrifugation experiments were used to correlate activation and binding affinity. PKR activation requires both 5'- and 3'-single-stranded tails but the triphosphate is dispensable. Activation potency and binding affinity decrease as the ssRNA tails are truncated and activation is abolished in cases where the binding affinity is strongly reduced. These results indicate that the single-stranded regions bind to PKR and support a model where ss-dsRNA induced dimerization is required but not sufficient to activate the kinase. The length of the duplex regions in several natural RNA activators of PKR is below the minimum of 30 bp required for activation and similar interactions with single-stranded regions may contribute to PKR activation in these cases.
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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.