دورية أكاديمية
ADAR1-dependent editing regulates human β cell transcriptome diversity during inflammation
| 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: | Szymczak, Florian, Cohen-Fultheim, Roni, Thomaidou, Sofia, de Brachène, Alexandra Cooman, Castela, Angela, Colli, Maikel, Marchetti, Piero, Levanon, Erez, Eizirik, Decio, Zaldumbide, Arnaud |
| سنة النشر: | 2022 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | RNA editing, T1D (type 1 diabetes), beta cell (β cell), inflammation, transcriptome |
| 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 βcell transcriptome under inflammatory conditions. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36518246; info:eu-repo/semantics/altIdentifier/wos/WOS:000898155500001; volume:13; firstpage:1058345; journal:FRONTIERS IN ENDOCRINOLOGY; info:eu-repo/grantAgreement/EC/H2020/945268; https://hdl.handle.net/11568/1169490Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85144067862 |
| DOI: | 10.3389/fendo.2022.1058345 |
| الإتاحة: | https://doi.org/10.3389/fendo.2022.1058345Test https://hdl.handle.net/11568/1169490Test |
| رقم الانضمام: | edsbas.D0894C92 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fendo.2022.1058345 |
|---|