When one becomes many-Alternative splicing in β-cell function and failure

Pancreatic β-cell dysfunction and death are determinant events in type 1 diabetes (T1D), but the molecular mechanisms behind β-cell fate remain poorly understood. Alternative splicing is a post-transcriptional mechanism by which a single gene generates different mRNA and protein isoforms, expanding the transcriptome complexity and enhancing protein diversity. Neuron-specific and certain serine/arginine-rich RNA binding proteins (RBP) are enriched in β-cells, playing crucial roles in the regulation of insulin secretion and β-cell survival. Moreover, alternative exon networks, regulated by inflammation or diabetes susceptibility genes, control key pathways and processes for the correct function and survival of β-cells. The challenge ahead of us is to understand the precise role of alternative splicing regulators and splice variants on β-cell function, dysfunction and death and develop tools to modulate it.