ArticlePloS one2013
Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 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
- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- A tRNA gene potential to activate interferon signaling involves selective termination and is suppressible by La protein/SSB.Nucleic acids research · 2025Article
- Effective recognition of double-stranded RNA does not require activation of cellular inflammation.Science advances · 2025Article
- Mapping Current Studies of tRNA Fragments onto Disease Landscape.Biomolecules · 2025Review
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- Immunogenicity ofAccounts of chemical research · 2021Review
- Mucosal immunity and tRNA, tRF, and tiRNA.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Regulation and Function of RNA Pseudouridylation in Human Cells.Annual review of genetics · 2020Review
- 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
- Crystal structure of an adenovirus virus-associated RNA.Nature communications · 2019Article
- Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs.Scientific reports · 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
- Nucleoside modifications in the regulation of gene expression: focus on tRNA.Cellular and molecular life sciences : CMLS · 2016Review
- 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
- Silent Polymorphisms: Can the tRNA Population Explain Changes in Protein Properties?Life (Basel, Switzerland) · 2016Review
- Mechanistic Analysis of Activation of the Innate Immune Sensor PKR by Bacterial RNA.Journal of molecular biology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5'-end triphosphate-a signature of certain viral and bacterial transcripts-confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe)in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in 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.