The physiology of alternative splicing

Alternative splicing is a substantial contributor to the high complexity of transcriptomes of multicellular eukaryotes. In this Review, we discuss the accumulated evidence that most of this complexity is reflected at the protein level and fundamentally shapes the physiology and pathology of organisms. This notion is supported not only by genome-wide analyses but, mainly, by detailed studies showing that global and gene-specific modulations of alternative splicing regulate highly diverse processes such as tissue-specific and species-specific cell differentiation, thermal regulation, neuron self-avoidance, infrared sensing, the Warburg effect, maintenance of telomere length, cancer and autism spectrum disorders (ASD). We also discuss how mastering the control of alternative splicing paved the way to clinically approved therapies for hereditary diseases.

Automated summary

Alternative splicing is a significant contributor to the complexity of multicellular eukaryotic transcriptomes, shaping the physiology and pathology of organisms at the protein level. It regulates diverse processes such as cell differentiation, thermal regulation, neuron self-avoidance, infrared sensing, Warburg effect, telomere length maintenance, cancer, and autism spectrum disorders. Additionally, understanding the control of alternative splicing has paved the way for clinical therapies of hereditary diseases.