RNA-Binding Proteins Regulate Cardiovascular Disease Progression Through Alternative Splicing and Alternative Polyadenylation.

Abstract

Alternative splicing (AS) and alternative polyadenylation (APA) are crucial post-transcriptional mechanisms enhancing transcriptomic and proteomic diversity. Dysregulation of AS and APA is pivotal in cardiovascular disease pathogenesis. This review focuses on RNA-binding proteins (RBPs) orchestrating AS and APA interplay in cardiovascular gene expression, particularly in cardiovascular diseases (CVDs) like atherosclerosis, heart failure, myocardial fibrosis, and ventricular remodeling. AS and APA exhibit intricate crosstalk, with RBPs influencing both processes. Key RBPs play mechanistic roles in immune regulation, calcium handling, and fibrotic signaling in CVDs. Additional regulatory factors such as non-coding RNAs, microbial influences, and redox signaling further modulate RBP activity and AS/APA outcomes. Targeting RBP-mediated AS and APA presents a promising therapeutic approach for CVDs, despite challenges related to specificity, regulatory complexity, and validation in human models. Future research should delve into cell-type-specific profiles and preclinical efficacy to advance precision treatments.