ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Diabetes Obes Metab. 2018 Sep;20 Suppl 2(Suppl 2):77-87. doi: 10.1111/dom.13388.
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.
胰岛β细胞功能障碍和死亡是 1 型糖尿病(T1D)的决定因素,但β细胞命运背后的分子机制仍知之甚少。选择性剪接是一种转录后机制,通过该机制,单个基因产生不同的 mRNA 和蛋白质异构体,从而扩大转录组的复杂性并增强蛋白质的多样性。神经元特异性和某些丝氨酸/精氨酸丰富的 RNA 结合蛋白(RBP)在β细胞中富集,在调节胰岛素分泌和β细胞存活方面发挥着关键作用。此外,由炎症或糖尿病易感性基因调节的选择性外显子网络控制着β细胞正确功能和存活的关键途径和过程。我们面临的挑战是要了解选择性剪接调节剂和剪接变体对β细胞功能、功能障碍和死亡的确切作用,并开发调节它们的工具。