Biochemical Profiling and Structural Basis of ADAR1-Mediated RNA Editing

ADAR1-mediated RNA editing suppresses the immunostimulatory potential of endogenous RNA. Deficiency in ADAR1 triggers inflammatory responses; however, the underlying mechanisms remain unclear. In this study, we overexpressed wild-type ADAR1 (ADAR1 WT) and various disease-associated ADAR1 variants in 293T cells to examine transcriptomic RNA editing events. We further compared how disease-associated ADAR1 variants fail to edit specific RNA substrates, potentially contributing to the activation of inflammatory pathways. To investigate the targets and RNA editing activity of ADAR1 and its mutants in the transcriptome, we overexpressed these ADAR1 variants in HEK293 cells. After 48 hours overexpression, we conducted RNA sequencing to identify adenosine-to-inosine (A-to-I) RNA editing events.