LncRNA ARGI Contributes to Virus‐Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN‐Stimulated Genes

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 disrup...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Advanced science Jg. 10; H. 25; S. e2300063 - n/a
Hauptverfasser: González‐Moro, Itziar, Garcia‐Etxebarria, Koldo, Mendoza, Luis Manuel, Fernández‐Jiménez, Nora, Mentxaka, Jon, Olazagoitia‐Garmendia, Ane, Arroyo, María Nicol, Sawatani, Toshiaki, Moreno‐Castro, Cristina, Vinci, Chiara, Op de Beek, Anne, Cnop, Miriam, Igoillo‐Esteve, Mariana, Santin, Izortze
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Germany John Wiley & Sons, Inc 01.09.2023
John Wiley and Sons Inc
Wiley
Schlagworte:
Cells
Diabetes Mellitus, Type 1
Disease
Gene expression
Genomes
Humans
Infections
Inflammation
Inflammation - metabolism
Insulin
Insulin-Secreting Cells
long non‐coding RNAs
pancreatic β cells
Pathogenesis
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Signal transduction
single nucleotide polymorphism
Student's t-test
Transcriptional Activation - genetics
type 1 diabetes
Viral infections
type 1 diabetes
viral infections
long non-coding RNAs
single nucleotide polymorphism
pancreatic β cells
ISSN:2198-3844, 2198-3844
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. Long non‐coding RNAs (lncRNAs) are emerging as regulators for several molecular processes that are important for human diseases. Herein, the function of a type 1 diabetes (T1D)‐associated lncRNA named ARGI is described. ARGI modulates the transcription of virus‐induced IFNβ and interfer on stimulated genes (ISGs) in pancreatic β cells in an allele‐specific manner.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202300063