LncRNA ARGI Contributes to Virus-Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN-Stimulated Genes
dc.contributor.author | González Moro, Itziar | |
dc.contributor.author | García Etxebarria, Koldo | |
dc.contributor.author | Mendoza Gómez, Luis Manuel | |
dc.contributor.author | Fernández Jiménez, Nora | |
dc.contributor.author | Mentxaka Salgado, Jon | |
dc.contributor.author | Olazagoitia Garmendia, Ane | |
dc.contributor.author | Nicol Arroyo, María | |
dc.contributor.author | Sawatani, Toshiaki | |
dc.contributor.author | Moreno Castro, Cristina | |
dc.contributor.author | Vinci, Chiara | |
dc.contributor.author | Op de Beek, Anne | |
dc.contributor.author | Cnop, Miriam | |
dc.contributor.author | Igoillo Esteve, Mariana | |
dc.contributor.author | Santín Gómez, Izortze | |
dc.date.accessioned | 2023-09-18T16:55:44Z | |
dc.date.available | 2023-09-18T16:55:44Z | |
dc.date.issued | 2023-09 | |
dc.identifier.citation | Advanced Science 10(25) : (2023) // Article ID 2300063 | es_ES |
dc.identifier.issn | 2198-3844 | |
dc.identifier.uri | http://hdl.handle.net/10810/62584 | |
dc.description.abstract | Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs) are located in non-coding regions of the human genome. Interestingly, SNPs in long non-coding RNAs (lncRNAs) may result in the disruption of their secondary structure, affecting their function, and in turn, the expression of potentially pathogenic pathways. In the present work, the function of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Inducer) is characterized. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic β cells and binds to CTCF to interact with the promoter and enhancer regions of IFNβ and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a change in its secondary structure. Interestingly, the T1D risk genotype induces hyperactivation of type I IFN response in pancreatic β cells, an expression signature that is present in the pancreas of T1D patients. These data shed light on the molecular mechanisms by which T1D-related SNPs in lncRNAs influence pathogenesis at the pancreatic β cell level and opens the door for the development of therapeutic strategies based on lncRNA modulation to delay or avoid pancreatic β cell inflammation in T1D. | es_ES |
dc.description.sponsorship | This work was supported by grants PID2019-104475GA-I00 funded by MCIN/AEI/10.13039/501100011033, and by the European Foundation for the Study of Diabetes (EFSD) – EFSD/JDRF/Lilly Programme on Type 1 Diabetes Research to I.S., the Fondation Franconphone pour la Recherche sur le Diabète (FFRD) to M.C. and M.I.E. M.C. acknowledges support by the Walloon Region SPW-EER (Win2Wal project BetaSource) and the Fonds National de la Recherche Scientifique (FRS-FNRS). I.G.M. is supported by a Predoctoral Fellowship Grants from the UPV/EHU (Universidad del País Vasco/Euskal Herriko Unibertsitatea). A.O.G. is supported by a post-doctoral grant from UPV/EHU (ESPDOC21/56, Universidad del País Vasco/Euskal Herriko Unibertsitatea), M.N.A. is a FRIA F.R.S-FNRS fellow. T.S. is supported by a Marie Skłodowska-Curie Actions Fellowship from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801505. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/801505 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-104475GA-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.title | LncRNA ARGI Contributes to Virus-Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN-Stimulated Genes | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202300063 | es_ES |
dc.identifier.doi | 10.1002/advs.202300063 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |
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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.