ADAR1-dependent editing regulates human β cell transcriptome diversity during inflammation

Front Endocrinol (Lausanne). 2022 Nov 28:13:1058345. doi: 10.3389/fendo.2022.1058345. eCollection 2022.


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.

Keywords: RNA editing; T1D (type 1 diabetes); beta cell (β cell); inflammation; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase* / genetics
  • Adenosine Deaminase* / metabolism
  • Diabetes Mellitus, Type 1*
  • Humans
  • Inflammation / genetics
  • Insulin-Secreting Cells* / metabolism
  • Interferon Type I* / genetics
  • Interferon Type I* / metabolism
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Transcriptome


  • Adenosine Deaminase
  • Interferon Type I
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA-Binding Proteins
  • ADAR protein, human