Alternative Splicing in CKD

作者：Stevens Megan; Oltean Sebastian^*

来源：Journal of the American Society of Nephrology, 2016, 27(6): 1596-1603.

DOI：10.1681/ASN.2015080908

Alternative splicing (AS) has emerged in the postgenomic era as one of the main drivers of proteome diversity, with >= 94% of mu ltiexon genes alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and is a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites, or regulatory sequences. Additionally, compared with the physiologic state, disease often associates with an abnormal proportion of splice isoforms (or novel isoforms), without an apparent driver mutation. It is therefore essential to study how AS is regulated in physiology, how it contributes to pathogenesis, and whether we can manipulate faulty splicing for therapeutic advantage. Although the disease most commonly linked to deregulation of AS in several genes is cancer, many reports detail pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies. A plethora of splice variants have been implicated in CKDs as well. In this review, we describe examples of these CKD-associated splice variants and ideas on how to manipulate them for therapeutic benefit.

• 出版日期2016-6