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 |
| المساهمون: |
Juvenile Diabetes Research Foundation Netherlands, Diabetes Fonds |
| المصدر: |
Frontiers in Endocrinology ; volume 13 ; ISSN 1664-2392 |
| بيانات النشر: |
Frontiers Media SA |
| سنة النشر: |
2022 |
| المجموعة: |
Frontiers (Publisher - via CrossRef) |
| مصطلحات موضوعية: |
Endocrinology, Diabetes and Metabolism |
| الوصف: |
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 IFNγ/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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| DOI: |
10.3389/fendo.2022.1058345 |
| DOI: |
10.3389/fendo.2022.1058345/full |
| الإتاحة: |
https://doi.org/10.3389/fendo.2022.1058345Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.41D7D8B1 |
| قاعدة البيانات: |
BASE |
