Role of RBM20 alternative splicing factor for the regulation of neuronal functions

Neuronal circuits consist of specialized cell types with unique structural and functional properties that shape nervous system function. Precise coordination of molecular programs and neuronal growth govern the formation, maintenance, and adaptation of these features, yet the regulatory mechanisms remain poorly understood. Alternative splicing has emerged as a key layer of neuronal cell-type-specific gene regulation during development. To uncover novel neuronal cell-type-specific RNA regulators, we systematically investigated expression of RNA recognition motif (RRM)-containing proteins in neuronal cell classes of the mouse neocortex. Surprisingly, we found the RNA-binding protein 20 (RBM20), an alternative splicing regulator associated with dilated cardiomyopathy, to be mainly expressed in cortical parvalbumin-positive interneurons and glutamatergic mitral cells of the mouse olfactory bulb. Genome-wide mapping of RBM20 target mRNAs revealed that neuronal RBM20 binds intronic regions, regulating transcript isoforms and transcript abundance of ion channels, cytoskeletal components, and proteins involved in synaptic function. Understanding the mechanisms involving cell type-specific RNA-binding proteins may offer potential for advancing therapeutic approaches in neurological diseases, leading to targeted interventions and improved treatment possibilities.