Poison exons in neurodevelopment and disease

Poison exons are naturally occurring, highly conserved alternative exons that contain a premature termination codon. Inclusion of a poison exon in a transcript targets the transcript for nonsense mediated decay, decreasing the amount of protein produced. Poison exons are proposed to play an important role in tissue-specific expression, development and autoregulation of gene expression. Recently, several studies that performed systematic investigations of alternative splicing in the brain have highlighted the abundance of transcripts containing poison exons, some of which are spliced in a cell type-specific manner. Pathogenic variants in or near poison exons that result in aberrant splicing have been identified in several genes including FLNA, SCN1A and SNRPB. Improved understanding of the role of poison exons in development and disease may present opportunities to solve previously undiagnosed disease and to develop therapeutic approaches in the future.