Alternative splicing of neuronal genes: new mechanisms and new therapies

Dynamic changes in alternative splicing during the life cycle of neurons support development and plasticity, and are implicated in disease pathology. Cell-specific alternative splicing programs coordinate exon selection across networks of functionally connected genes. In this opinion piece, we highlight recent publications that identify some of the molecular mechanisms-RNA and DNA binding proteins and epigenetic modifications-which direct cell-specific exon selection during pre-mRNA splicing. Aberrant splicing patterns are signature features of a growing number of diseases of the nervous system. Recent publications demonstrate the value of delineating basic mechanisms that dictate exon choice to inform the development of new therapeutic strategies that correct or compensate for damaging deficits in alternative splicing.