Alternative RNA Splicing in Cardiac Diseases

Alternative splicing (AS), a critical process for gene expression regulation, allows a single precursor RNA to produce multiple transcript variants. Alterations in exon exclusion, intron retention, or the selection of alternative splice sites modify transcript isoforms, which can consequently affect RNA molecules, including mRNA and non-coding RNAs, in terms of their localization, regulation, and overall function. In the cardiovascular system, AS of transcripts of sarcomere, ion channel, and cell signaling protein genes, as well as long non-coding RNAs, can contribute to the development of cardiovascular diseases. In addition, multiple hereditary heart-related diseases are caused by mutations associated with AS. In this review, we discuss how AS regulates individual genes and global biological processes, thereby diversifying the expression patterns of target genes and playing critical roles in cardiovascular diseases. We also review the application of AS in the design of innovative therapeutic approaches.