Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart

Cardiac physiology and pathology have been extensively explored at the transcriptional level, but are less understood at the translational level. Translation of mRNA to protein is the final step in the central dogma for protein synthesis. Translation machinery includes a family of essential “housekeeping” factors and enzymes required for mRNA translation. These translation factors ensure the accurate processing of mRNA to protein according to the genetic code and maintain the optimal quality and quantity of cellular proteins for normal cardiac function. Translation factors also control the efficiency, speed, and fidelity of protein production and participate in cardiac pathological remodeling under stress conditions. This review summarizes discoveries of the pathophysiological function and molecular mechanism of translational control in cardiac health and disease. Translational control has extensive crosstalk to other processes such as transcriptional regulation, mi-tochondrial metabolism, and sarcomere homeostasis. We discuss the translational regu-lation directed by specific regulatory factors in cardiac physiology and the etiology of heart disease when they undergo genetic mutation, expression dysregulation, or func-tional alteration. Because transcript-specific translational regulation of pathological and protective proteins occurs in heart disease, target-selective translation inhibitors and enhancers can be developed. These inhibitors and enhancers provide valuable insights into novel therapeutic targets and RNA-based drug development for heart disease treatment.