ArticleRNA (New York, N.Y.)2012
Activation of PKR by RNA misfolding: HDV ribozyme dimers activate PKR.
Article in RNA (New York, N.Y.), 2012. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 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
- Hepatitis Delta Virus and Hepatocellular Carcinoma.Pathogens (Basel, Switzerland) · 2024Review
- HDV Pathogenesis: Unravelling Ariadne's Thread.Viruses · 2021Review
- Review
- Structural Insights into RNA Dimerization: Motifs, Interfaces and Functions.Molecules (Basel, Switzerland) · 2020Review
- 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
- Article
- Interaction of PKR with single-stranded RNA.Scientific reports · 2017Article
- Enhancing titres of therapeutic viral vectors using the transgene repression in vector production (TRiP) system.Nature communications · 2017Article
- Activation of PKR by short stem-loop RNAs containing single-stranded arms.RNA (New York, N.Y.) · 2016Article
- Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR.Accounts of chemical research · 2016Review
- Article
- Regulation of PKR by RNA: formation of active and inactive dimers.Biochemistry · 2015Article
- Mechanistic Analysis of Activation of the Innate Immune Sensor PKR by Bacterial RNA.Journal of molecular biology · 2015Article
- Animal models of chronic hepatitis delta virus infection host-virus immunologic interactions.Pathogens (Basel, Switzerland) · 2015Review
- Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR.PloS one · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Protein Kinase R (PKR), the double-stranded RNA (dsRNA)-activated protein kinase, plays important roles in innate immunity. Previous studies have shown that PKR is activated by long stretches of dsRNA, RNA pseudoknots, and certain single-stranded RNAs; however, regulation of PKR by RNAs with globular tertiary structure has not been reported. In this study, the HDV ribozyme is used as a model of a mostly globular RNA. In addition to a catalytic core, the ribozyme contains a peripheral 13-bp pairing region (P4), which, upon shortening, affects neither the catalytic activity of the ribozyme nor its ability to crystallize. We report that the HDV ribozyme sequence alone can activate PKR. To elucidate the RNA structural basis for this, we prepared a number of HDV variants, including those with shortened or lengthened P4 pairing regions, with the anticipation that lengthening the P4 extension would yield a more potent activator since it would offer more base pairs of dsRNA. Surprisingly, the variant with a shortened P4 was the most potent activator. Through native gel mobility and enzymatic structure mapping experiments we implicate misfolded HDV ribozyme dimers as the PKR-activating species, and show that the shortened P4 leads to enhanced occupancy of the RNA dimer. These observations have implications for how RNA misfolding relates to innate immune response and human disease.
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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.