التفاصيل البيبلوغرافية
| العنوان: |
ADAR1-dependent editing regulates human β cell transcriptome diversity during inflammation. |
| المؤلفون: |
Szymczak, Florian, Cohen-Fultheim, Roni, Thomaidou, Sofia, de Brachène, Alexandra Coomans, Castela, Angela, Colli, Maikel, Marchetti, Piero, Levanon, Erez, Eizirik, Decio, Zaldumbide, Arnaud |
| المصدر: |
Frontiers in Endocrinology; 11/29/2022, Vol. 13, p1-12, 12p |
| مصطلحات موضوعية: |
ADENOSINES, TYPE I interferons, DOUBLE-stranded RNA, TYPE 1 diabetes, TRANSCRIPTOMES, RNA editing, PANCREATIC enzymes |
| مستخلص: |
Introduction: Enterovirus infection has long been suspected as a possible trigger for type 1 diabetes. Upon infection, viral double-stranded RNA (dsRNA) is recognized by membrane and cytosolic sensors that orchestrate type I interferon signaling and the recruitment of innate immune cells to the pancreatic islets. In this context, adenosine deaminase acting on RNA 1 (ADAR1) editing plays an important role in dampening the immune response by inducing adenosine mispairing, destabilizing the RNA duplexes and thus preventing excessive immune activation. Methods: Using high-throughput RNA sequencing data from human islets and EndoC-βH1 cells exposed to IFNα or IFNg/IL1β, we evaluated the role of ADAR1 in human pancreatic β cells and determined the impact of the type 1 diabetes pathophysiological environment on ADAR1-dependent RNA editing. Results: We show that both IFNα and IFNγ/IL1β stimulation promote ADAR1 expression and increase the A-to-I RNA editing of Alu-Containing mRNAs in EndoC-βH1 cells as well as in primary human islets. Discussion: We demonstrate that ADAR1 overexpression inhibits type I interferon response signaling, while ADAR1 silencing potentiates IFNα effects. In addition, ADAR1 overexpression triggers the generation of alternatively spliced mRNAs, highlighting a novel role for ADAR1 as a regulator of the β cell transcriptome under inflammatory conditions. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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