Abstract
Alternative splicing (AS) is a fundamental post-transcriptional regulatory mechanism that dramatically expands the proteomic diversity encoded by a limited genome. This process is tightly controlled by a complex interplay between cis-acting RNA elements and trans-acting RNA-binding proteins (RBPs). Dysregulation of AS has been implicated in a wide spectrum of human diseases, including cancer, neurodegenerative disorders, and cardiovascular pathologies. RBPs act as key molecular switches, recognizing specific RNA sequences or structures to either promote or repress the inclusion or exclusion of exons, thereby fine-tuning gene expression and cellular function. This review, published in January 2024, focuses on elucidating the intricate mechanisms by which RBPs modulate AS and how this dysregulation contributes to disease pathogenesis. We highlight recent advances in understanding RBP-target interactions, the role of RBP networks, and the functional consequences of aberrant AS events in various disease contexts. Furthermore, we discuss emerging therapeutic strategies that target the RBP-AS axis for disease intervention. Understanding this complex regulatory network is crucial for developing novel diagnostic markers and targeted therapies for diseases driven by splicing abnormalities.