RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond [RNA-seq]

RNA modifications, including adenosine-to-inosine (A-to-I) editing, are fundamental for normal brain physiology, as they participate in multiple biological processes and pathological conditions. These modifications can alter RNA secondary structures and affinity for RNA-binding proteins, thereby influencing RNA processing mechanisms such as alternative splicing. In this study, we investigated A-to-I RNA editing and its impact on alternative splicing regulation in the mouse brain using ADAR enzyme-deficient mice. We analyzed the brain transcriptome of ADAR2 knockout (Adar2-/-Gria2R/R), as well as double ADAR1 catalytically inactive / ADAR2 knockout (Adar1E861A/E861A Ifih-/- Adar2-/-Gria2R/R) mice compared to wild-type controls, identifying alternative splicing events associated with the absence of ADAR1 and ADAR2 specific A-to-I editing. Overall design: Total RNA from whole brains from adult 3–4-month-old male mice was used for RNA-seq as described in the Methods section of this publication. Three biological replicates for each genotype were sequenced. ADAR2 knockout (Adar2-/-Gria2R/R), double ADAR1 catalytically inactive/ADAR2 knockout (Adar1E861A/E861A Ifih-/-Adar2-/-Gria2R/R) and wild-type controls. All mice were C57BL/6J on a background.