ArticleProceedings of the National Academy of Sciences of the United States of America2015
Potential role for snoRNAs in PKR activation during metabolic stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 114 citations in OpenAlex.
- Box C/D snoRNPs and MDT-15/MED15 regulate mitochondrial surveillance and mitophagy via fatty acid metabolism.GeroScience · 2026Article
- Genome-wide profiling of RNA 2'-O-methylation in neurons and identification of orphan snoRNA targets.Research square · 2026Article
- Small Nucleolar RNAs (snoRNAs) in Cancer: From Biogenesis to Clinical Potential.OncoTargets and therapy · 2026Review
- Genome-wide profiling of RNA 2'-bioRxiv : the preprint server for biology · 2025Article
- Systematic mapping of small nucleolar RNA interactions in human cells.RNA biology · 2025Article
- Unveiling Small Non-Coding RNA Dynamics During Recombinant Adeno-Associated Virus Production.Biotechnology journal · 2025Article
- Footprints in the Sno: investigating the cellular and molecular mechanisms of SNORD116.Open biology · 2025Review
- SNORD80-guided 2'-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024Review
- PKR Mediates the Mitochondrial Unfolded Protein Response through Double-Stranded RNA Accumulation under Mitochondrial Stress.International journal of molecular sciences · 2024Article
- RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.BMC biology · 2024Article
- SnoRNAs: Exploring Their Implication in Human Diseases.International journal of molecular sciences · 2024Review
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- Intron Editing RevealsInternational journal of molecular sciences · 2023Article
- Control of protein synthesis through mRNA pseudouridylation by dyskerin.Science advances · 2023Article
- PKR activation in mitochondrial unfolded protein response-mitochondrial dsRNA might do the trick.Frontiers in cell and developmental biology · 2023Article
- Ribosome changes reprogram translation for chemosurvival in G0 leukemic cells.Science advances · 2022Article
- The Role and Therapeutic Potential of the Integrated Stress Response in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering.The Journal of cell biology · 2022Article
- Protein-RNA Interactome Analysis Reveals Wide Association of Kaposi's Sarcoma-Associated Herpesvirus ORF57 with Host Noncoding RNAs and Polysomes.Journal of virology · 2022Article
19 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
Abstract
Protein kinase RNA-activated (PKR) has long been known to be activated by viral double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in mice PKR is also activated by metabolic stress in the absence of viral infection, and this requires a functional kinase domain, as well as a functional dsRNA-binding domain. The endogenous cellular RNA that potentially leads to PKR activation during metabolic stress is unknown. We investigated this question using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we identified endogenous RNA that interacts with PKR after induction of metabolic stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed that the majority of enriched RNAs that interacted with WT PKR (≥twofold, false discovery rate ≤ 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of PKR in extracts of UV-cross-linked cells, followed by RT-qPCR, confirmed that snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM samples. We also demonstrated that a subset of identified snoRNAs bind and activate PKR in vitro; the presence of a 5'-triphosphate enhanced PKR activity compared with the activity with a 5'-monophosphate, for some, but not all, snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR. Our results suggest an unprecedented and unexpected model whereby snoRNAs play a role in the activation of PKR under metabolic stress.
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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.