Hause, A. M. et al. Safety monitoring of bivalent COVID-19 mRNA vaccine booster doses among persons aged >/=12 years—United States, August 31-October 23, 2022. MMWR Morb. Mortal Wkly Rep. 71, 1401–1406 (2022).
Winkle, M., El-Daly, S. M., Fabbri, M. & Calin, G. A. Noncoding RNA therapeutics—challenges and potential solutions. Nat Rev. Drug Discov. 20, 629–651 (2021).
Enuka, Y. et al. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res. 44, 1370–1383 (2016).
Zhang, Y. et al. The biogenesis of nascent circular RNAs. Cell Rep. 15, 611–624 (2016).
Fischer, J. W., Busa, V. F., Shao, Y. & Leung, A. K. L. Structure-mediated RNA decay by UPF1 and G3BP1. Mol. Cell. 78, 70–84.e76 (2020).
Liu, C. X. et al. Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell 177, 865–880.e821 (2019).
Wesselhoeft, R. A. et al. RNA circularization diminishes immunogenicity and can extend translation duration in vivo. Mol. Cell. 74, 508–520.e504 (2019).
Liu, C. X. et al. RNA circles with minimized immunogenicity as potent PKR inhibitors. Mol. Cell. 82, 420–434.e426 (2022).
Liu, C. X. & Chen, L. L. Circular RNAs: characterization, cellular roles, and applications. Cell 185, 2390 (2022).
Bou-Nader, C., Gordon, J. M., Henderson, F. E. & Zhang, J. The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators. RNA 25, 539–556 (2019).
Cao, S. S., Song, B. & Kaufman, R. J. PKR protects colonic epithelium against colitis through the unfolded protein response and prosurvival signaling. Inflamm. Bowel Dis. 18, 1735–1742 (2012).
Grolleau, A., Kaplan, M. J., Hanash, S. M., Beretta, L. & Richardson, B. Impaired translational response and increased protein kinase PKR expression in T cells from lupus patients. J. Clin. Invest. 106, 1561–1568 (2000).
Rath, E. et al. Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis of intestinal inflammation. Gut 61, 1269–1278 (2012).
Zheng, X. & Bevilacqua, P. C. Activation of the protein kinase PKR by short double-stranded RNAs with single-stranded tails. RNA 10, 1934–1945 (2004).
Ingrand, S. et al. The oxindole/imidazole derivative C16 reduces in vivo brain PKR activation. FEBS Lett. 581, 4473–4478 (2007).
Mouton-Liger, F. et al. PKR downregulation prevents neurodegeneration and β-amyloid production in a thiamine-deficient model. Cell Death Dis. 6, e1594 (2015).
Watanabe, T. et al. Therapeutic effects of the PKR inhibitor C16 suppressing tumor proliferation and angiogenesis in hepatocellular carcinoma in vitro and in vivo. Sci. Rep. 10, 5133 (2020).
Griffiths, C. E. M., Armstrong, A. W., Gudjonsson, J. E., & Barker, J. Psoriasis. Lancet 397, 1301–1315 (2021).
Moldovan, L. I. et al. High-throughput RNA sequencing from paired lesional- and non-lesional skin reveals major alterations in the psoriasis circRNAome. BMC Med. Genomics 12, 174 (2019).
Moldovan, L. I. et al. Characterization of circular RNA transcriptomes in psoriasis and atopic dermatitis reveals disease-specific expression profiles. Exp. Dermatol. 30, 1187–1196 (2021).
Seeler, S. et al. Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment. PLoS ONE 17, e0275219 (2022).
Swindell, W. R. et al. Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis. Genome Med. 9, 24 (2017).
Obi, P. & Chen, Y. G. The design and synthesis of circular RNAs. Methods 196, 85–103 (2021).
Puttaraju, M. & Been, M. D. Group I permuted intron-exon (PIE) sequences self-splice to produce circular exons. Nucleic Acids Res. 20, 5357–5364 (1992).
Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).
Guo, S. K., Nan, F., Liu, C. X., Yang, L. & Chen, L. L. Mapping circular RNA structures in living cells by SHAPE-MaP. Methods 196, 47–55 (2021).
Kuhen, K. L. et al. Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog. Genomics 36, 197–201 (1996).
Samuel, C. E. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J. Biol. Chem. 268, 7603–7606 (1993).
Wu, M. et al. lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription. Science 373, 547–555 (2021).
Yang, X. W. et al. MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair. Nat. Commun. 13, 5808 (2022).
Hummert, J. et al. Photobleaching step analysis for robust determination of protein complex stoichiometries. Mol. Biol. Cell. 32, ar35 (2021).
Yuan, J., He, K., Cheng, M., Yu, J. & Fang, X. Analysis of the steps in single-molecule photobleaching traces by using the hidden Markov model and maximum-likelihood clustering. Chem. Asian J. 9, 2303–2308 (2014).
Nallagatla, S. R., Toroney, R. & Bevilacqua, P. C. Regulation of innate immunity through RNA structure and the protein kinase PKR. Curr. Opin. Struct. Biol. 21, 119–127 (2011).
Heinicke, L. A., Nallagatla, S. R., Hull, C. M. & Bevilacqua, P. C. RNA helical imperfections regulate activation of the protein kinase PKR: effects of bulge position, size, and geometry. RNA 17, 957–966 (2011).
Yan, Y., Tao, H., He, J. & Huang, S. Y. The HDOCK server for integrated protein-protein docking. Nat. Protoc. 15, 1829–1852 (2020).
Husain, B., Hesler, S. & Cole, J. L. Regulation of PKR by RNA: formation of active and inactive dimers. Biochemistry 54, 6663–6672 (2015).
Mayo, C. B. et al. Structural basis of protein kinase R autophosphorylation. Biochemistry 58, 2967–2977 (2019).
Dörner, T. & Furie, R. Novel paradigms in systemic lupus erythematosus. Lancet 393, 2344–2358 (2019).
Tsokos, G. C., Lo, M. S., Costa Reis, P. & Sullivan, K. E. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat. Rev. Rheumatol. 12, 716–730 (2016).
van der Fits, L. et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol. 182, 5836–5845 (2009).
Taylor, S. S., Haste, N. M. & Ghosh, G. PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking. Cell 122, 823–825 (2005).
Ma, X. K. et al. CIRCexplorer3: a CLEAR pipeline for direct comparison of circular and linear RNA expression. Genom. Proteom. Bioinform. 17, 511–521 (2019).
Futschik, M. E. & Carlisle, B. Noise-robust soft clustering of gene expression time-course data. J. Bioinform. Comput. Biol. 3, 965–988 (2005).
Kumar, L. & M, E. F. Mfuzz: a software package for soft clustering of microarray data. Bioinformation 2, 5–7 (2007).
Lande, R. & Gilliet, M. Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann. N. Y. Acad. Sci. 1183, 89–103 (2010).
Chiricozzi, A., Romanelli, P., Volpe, E., Borsellino, G. & Romanelli, M. Scanning the immunopathogenesis of psoriasis. Int. J. Mol. Sci. 19, 179 (2018).
Yang, Y. L. et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14, 6095–6106 (1995).
Nestle, F. O. et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J. Exp. Med. 202, 135–143 (2005).
Rácz, E. et al. Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes. Br. J. Dermatol. 164, 838–847 (2011).
Zhang, L. J. et al. Antimicrobial peptide LL37 and MAVS signaling drive interferon-β production by epidermal keratinocytes during skin injury. Immunity 45, 119–130 (2016).
Chen, L. L. et al. A guide to naming eukaryotic circular RNAs. Nat. Cell Biol. 25, 1–5 (2023).
Zhang, X. O. et al. Complementary sequence-mediated exon circularization. Cell 159, 134–147 (2014).
Naidu, G. S. et al. A combinatorial library of lipid nanoparticles for cell type-specific mRNA delivery. Adv. Sci. 10, e2301929 (2023).
Jones, S. A. et al. GILZ regulates Th17 responses and restrains IL-17-mediated skin inflammation. J. Autoimmun. 61, 73–80 (2015).
Fredriksson, T. & Pettersson, U. Severe psoriasis-oral therapy with a new retinoid. Dermatologica 157, 238–244 (1978).
Langley, R. G. & Ellis, C. N. Evaluating psoriasis with psoriasis area and severity index, psoriasis global assessment, and lattice system physician’s global assessment. J. Am. Acad. Dermatol. 51, 563–569 (2004).
Chen, Y. G. et al. N6-methyladenosine modification controls circular RNA immunity. Mol. Cell. 76, 96–109.e109 (2019).
Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 185, 1728–1744.e1716 (2022).
Gal-Ben-Ari, S., Barrera, I., Ehrlich, M. & Rosenblum, K. PKR: a kinase to remember. Front. Mol. Neurosci. 11, 480 (2018).
Tronel, C., Page, G., Bodard, S., Chalon, S. & Antier, D. The specific PKR inhibitor C16 prevents apoptosis and IL-1beta production in an acute excitotoxic rat model with a neuroinflammatory component. Neurochem. Int. 64, 73–83 (2014).
Chang, R. C. et al. Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2alpha in neuronal degeneration. J. Neurochem. 83, 1215–1225 (2002).
Stern, E., Chinnakkaruppan, A., David, O., Sonenberg, N. & Rosenblum, K. Blocking the eIF2alpha kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory. J. Neurosci. 33, 2517–2525 (2013).
Zhu, P. J. et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-gamma-mediated disinhibition. Cell 147, 1384–1396 (2011).
Feng, X. et al. Circular RNA aptamers ameliorate AD-relevant phenotypes by targeting PKR. Preprint at bioRxiv https://doi.org/10.1101/2024.03.27.583257 (2024).
Kaushik, S. B. & Lebwohl, M. G. Psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents. J. Am. Acad. Dermatol. 80, 27–40 (2019).
Manfreda, V., Esposito, M., Campione, E., Bianchi, L. & Giunta, A. Apremilast efficacy and safety in a psoriatic arthritis patient affected by HIV and HBV virus infections. Postgrad. Med. 131, 239–240 (2019).
Guimaraes, C. P. et al. Site-specific C-terminal and internal loop labeling of proteins using sortase-mediated reactions. Nat. Protoc. 8, 1787–1799 (2013).
Donovan, J., Rath, S., Kolet-Mandrikov, D. & Korennykh, A. Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery. RNA 23, 1660–1671 (2017).
Xiao, M. S. & Wilusz, J. E. An improved method for circular RNA purification using RNase R that efficiently removes linear RNAs containing G-quadruplexes or structured 3′ ends. Nucleic Acids Res. 47, 8755–8769 (2019).
Matsui, T., Tanihara, K. & Date, T. Expression of unphosphorylated form of human double-stranded RNA-activated protein kinase in Escherichia coli. Biochem. Biophys. Res. Commun. 284, 798–807 (2001).
Smola, M. J., Rice, G. M., Busan, S., Siegfried, N. A. & Weeks, K. M. Selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis. Nat. Protoc. 10, 1643–1669 (2015).
Senavirathne, G. et al. Widespread nuclease contamination in commonly used oxygen-scavenging systems. Nat. Methods 12, 901–902 (2015).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357–360 (2015).
Kim, D. & Salzberg, S. L. TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol. 12, R72 (2011).
Zhang, Y., Wang, J. & Xiao, Y. 3dRNA: 3D structure prediction from linear to circular RNAs. J. Mol. Biol. 434, 167452 (2022).
Othniel, J. “doi: 10.17632/j6fmfjrc5y.1”, Mendeley Data, V1. Mendely Data https://doi.org/10.17632/94jg7jkt6n.1 (2020).
Guo, S. K. et al. Therapeutic Application of Circular RNA Aptamers in a Mouse Model of Psoriasis (Gene Expression Omnibus, 2024); http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE248680
Weidinger S., Rodriguez E., Tsoi L. C. & Gudjonsson J. Atopic Dermatitis, Psoriasis and Healthy Control RNA-seq Cohort (Gene Expression Omnibus, 2019); https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121212
