LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes
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 t...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202300063 |
| _version_ | 1797692697986727936 |
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| author | Itziar González‐Moro Koldo Garcia‐Etxebarria Luis Manuel Mendoza Nora Fernández‐Jiménez Jon Mentxaka Ane Olazagoitia‐Garmendia María Nicol Arroyo Toshiaki Sawatani Cristina Moreno‐Castro Chiara Vinci Anne Op de Beek Miriam Cnop Mariana Igoillo‐Esteve Izortze Santin |
| author_facet | Itziar González‐Moro Koldo Garcia‐Etxebarria Luis Manuel Mendoza Nora Fernández‐Jiménez Jon Mentxaka Ane Olazagoitia‐Garmendia María Nicol Arroyo Toshiaki Sawatani Cristina Moreno‐Castro Chiara Vinci Anne Op de Beek Miriam Cnop Mariana Igoillo‐Esteve Izortze Santin |
| author_sort | Itziar González‐Moro |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T02:32:21Z |
| format | Article |
| id | doaj.art-e0b08b72f8934629b39760d37febee3a |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T02:32:21Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-e0b08b72f8934629b39760d37febee3a2023-09-05T07:49:09ZengWileyAdvanced Science2198-38442023-09-011025n/an/a10.1002/advs.202300063LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated GenesItziar González‐Moro0Koldo Garcia‐Etxebarria1Luis Manuel Mendoza2Nora Fernández‐Jiménez3Jon Mentxaka4Ane Olazagoitia‐Garmendia5María Nicol Arroyo6Toshiaki Sawatani7Cristina Moreno‐Castro8Chiara Vinci9Anne Op de Beek10Miriam Cnop11Mariana Igoillo‐Esteve12Izortze Santin13Department of Biochemistry and Molecular Biology University of the Basque Country Leioa 48940 SpainBiodonostia Health Research Institute Gastrointestinal Genetics Group San Sebastián 20014 SpainDepartment of Biochemistry and Molecular Biology University of the Basque Country Leioa 48940 SpainBiocruces Bizkaia Health Research Institute Barakaldo 48903 SpainDepartment of Biochemistry and Molecular Biology University of the Basque Country Leioa 48940 SpainDepartment of Biochemistry and Molecular Biology University of the Basque Country Leioa 48940 SpainULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumULB Center for Diabetes Research Université Libre de Bruxelles Brussels 1070 BelgiumDepartment of Biochemistry and Molecular Biology University of the Basque Country Leioa 48940 SpainAbstract 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.https://doi.org/10.1002/advs.202300063long non‐coding RNAspancreatic β cellssingle nucleotide polymorphismtype 1 diabetesviral infections |
| spellingShingle | Itziar González‐Moro Koldo Garcia‐Etxebarria Luis Manuel Mendoza Nora Fernández‐Jiménez Jon Mentxaka Ane Olazagoitia‐Garmendia María Nicol Arroyo Toshiaki Sawatani Cristina Moreno‐Castro Chiara Vinci Anne Op de Beek Miriam Cnop Mariana Igoillo‐Esteve Izortze Santin LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes Advanced Science long non‐coding RNAs pancreatic β cells single nucleotide polymorphism type 1 diabetes viral infections |
| title | LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes |
| title_full | LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes |
| title_fullStr | LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes |
| title_full_unstemmed | LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes |
| title_short | LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes |
| title_sort | lncrna argi contributes to virus induced pancreatic β cell inflammation through transcriptional activation of ifn stimulated genes |
| topic | long non‐coding RNAs pancreatic β cells single nucleotide polymorphism type 1 diabetes viral infections |
| url | https://doi.org/10.1002/advs.202300063 |
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