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bioRxiv · 10.1101/2022.12.01.518685

The type 1 diabetes-associated lncRNA ARGI participates in virus-induced pancreatic beta cell inflammation.

Gonzalez-Moro, I.·Garcia-Etxebarria, K.·Mendoza, L. M.·Fernandez-Jiminez, N.·Mentxaka-Salgado, J.·Olazagoitia-Garmendia, A.·Arroyo, M. N.·Sawatani, T.·Op de Beek, A.·Cnop, M.·Igoillo-Esteve, M.·Santin, I.
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Abstract

Type 1 diabetes-associated single nucleotide polymorphisms are mainly located in non-coding regions of the human genome. Single nucleotide polymorphisms located in long non-coding RNAs may result in the disruption of their secondary structure, affecting their function. Here, we functionally characterized the virus-induced type 1 diabetes-associated lncRNA ARGI (Antiviral Response Gene Inducer). ARGI upregulation in pancreatic {beta} cells leads to the transcriptional activation of antiviral and pro-inflammatory genes. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic {beta} cells and binds to CTCF to interact with the regulatory regions of IFN{beta} and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the risk allele for type 1 diabetes in ARGI induces an hyperactivation of type I IFN response in {beta} cells, an expression signature that is present in the pancreas of diabetic patients. These data shed light on the molecular mechanisms by which type 1 diabetes-related single nucleotide polymorphisms in long non-coding RNAs influence pathogenesis at the pancreatic {beta} cell level.

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Gonzalez-Moro, I., Garcia-Etxebarria, K., Mendoza, L. M., Fernandez-Jiminez, N., Mentxaka-Salgado, J., Olazagoitia-Garmendia, A., Arroyo, M. N., Sawatani, T., Op de Beek, A., Cnop, M., Igoillo-Esteve, M., Santin, I.. 2022-12-02. The type 1 diabetes-associated lncRNA ARGI participates in virus-induced pancreatic beta cell inflammation.. https://doi.org/10.1101/2022.12.01.518685

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