RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond

RNA modifications in the brain can be essential for regulating the transcriptome and brain function. Our study unveils the landscape of different RNA modifications associated with splicing within the mouse brain. Focusing on inosine, known for its role in alternative splicing modulation and enriched in introns, we investigated its influence using mice lacking ADAR2 alone or in combination with catalytically inactive ADAR1. While some alternative splicing-regulatory roles of inosine and ADAR enzymes are established, we observe that altering ADAR2 and ADAR1/ADAR2 is associated with changes in alternative splicing and coincides with shifts in levels of other RNA modification. Through the utilization of an innovative approach, we identified novel candidate circular RNA profiles in wild-type and mutant mice and detected potential inosine sites within circular RNAs. Collectively, our findings underscore a complex interplay among RNA modifications, alternative splicing, circular RNAs in the mouse brain.