RNA Stability and Degradation: An Emerging Layer of Gene Regulation in Cardiac Disease

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide and is associated with profound pathological remodeling at both the cellular and molecular levels. Beyond transcriptional changes, post-transcriptional regulation—including RNA splicing, modification, nuclear export, and degradation—significantly expands the complexity of the eukaryotic transcriptome. Among these processes, RNA degradation remains comparatively understudied in cardiovascular biology. Traditionally viewed primarily as a quality-control mechanism that removes aberrant transcripts, including those containing premature termination codons, RNA degradation is now increasingly recognized as an active regulatory process that controls RNA quality, transcript abundance, and ultimately gene expression under both physiological and pathological conditions. Multiple mechanisms regulate RNA stability and degradation, including nonsense-mediated mRNA decay, RNA modifications, RNA-binding proteins, and noncoding RNAs, particularly microRNAs. These pathways have been extensively implicated in biological and disease processes including cancer and inflammation, and emerging evidence highlights their importance in cardiovascular homeostasis and disease. In the heart, altered RNA stability and degradation contribute to the regulation of cardiac contractility, ion-channel homeostasis, mitochondrial function, and inflammatory response. Recent advances in reporter-based RNA stability assays and metabolic RNA-labeling approaches have further enabled quantitative measurement of RNA degradation both in vitro and in vivo. In this review, we summarize the molecular mechanisms regulating RNA stability and degradation, discuss their emerging roles in cardiovascular physiology and disease, highlight recent technological advances for studying RNA turnover, and examine therapeutic strategies targeting RNA stability. Together, these advances establish RNA degradation as an important and potentially druggable target in CVD.