title: Alternative Splicing in CKD.
abstract: Alternative splicing (AS) has emerged in the postgenomic era as one of the main drivers of proteome diversity, with ≥94% of multiexon 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.
authors.affiliation: School of Physiology and Pharmacology, Faculty of Biomedical Sciences, and Academic Renal Unit, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Megan
authors.initials: M
authors.lastname: Stevens
authors.affiliation: School of Physiology and Pharmacology, Faculty of Biomedical Sciences, and Academic Renal Unit, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom sebastian.oltean@bristol.ac.uk.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Oltean
mesh_terms: D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D006801:Humans; D009154:Mutation; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: chronic kidney disease; gene expression; mRNA