Alternative Splicing in CKD.

Area of Science:

• Molecular Biology
• Genetics
• Disease Pathogenesis

Background:

• Alternative splicing (AS) is a key mechanism for generating proteome diversity, with over 94% of human multiexon genes undergoing this process.
• AS regulates cell phenotype and its deregulation is implicated in numerous diseases, including cancer, neuromuscular disorders, diabetes, cardiomyopathies, and chronic kidney diseases (CKDs).
• Pathogenic mutations in splicing factors or regulatory sequences are known drivers, but diseases can also arise from altered proportions of splice isoforms without apparent mutations.

Purpose of the Study:

• To review the role of AS in physiological processes and disease pathogenesis.
• To highlight CKD-associated splice variants and their contribution to disease.
• To explore therapeutic strategies for manipulating aberrant splicing.

Main Methods:

• Literature review of studies on alternative splicing in health and disease.
• Analysis of reported pathogenic splice variants in various diseases, with a focus on CKDs.
• Discussion of potential therapeutic interventions targeting faulty splicing.

Main Results:

• Alternative splicing is a fundamental process contributing significantly to human proteome diversity.
• Dysregulation of AS, including altered splice isoform ratios, is a common feature in various pathologies, notably CKDs.
• Specific splice variants are linked to CKD pathogenesis, presenting potential therapeutic targets.

Conclusions:

• Understanding AS regulation in physiology and disease is crucial.
• Targeting aberrant splicing mechanisms presents a promising avenue for therapeutic development in CKDs and other diseases.
• Further research into CKD-specific splice variants could lead to novel treatment strategies.