RNA-Binding Proteins as Critical Post-Transcriptional Regulators of Cardiac Regeneration

Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations.

Automated summary

Myocardial injury leads to cell death and heart failure. While the adult mammalian heart has limited regenerative capacity, early postnatal mammals and adult lower vertebrates can fully regenerate their hearts. RNA-binding proteins play a crucial role in regulating the survival and proliferation of cardiomyocytes following cardiac injury. By reprogramming various cellular processes, such as protein synthesis, metabolism, growth, and plasticity, RNA-binding proteins regulate heart regenerative capacity. Manipulating the activity of RNA-binding proteins may offer potential therapeutic interventions for cardiovascular disease.