Decoding Cardiac Maturation Program: Insights from RNA Splicing Regulation

Cardiomyocyte postnatal maturation is a critical step of the mammalian heart development continuum, involving a myriad of phenotypic changes at morphological, molecular, and functional levels. While the phenotypic hallmarks of cardiac maturation are well characterized, the molecular mechanisms that govern this maturation process are still poorly defined. This review aims to explore the recent findings on how post-transcriptional regulations orchestrate the fetal-to-adult cardiomyocyte transition and to highlight their clinical implications for cardiac diseases and regeneration medicine.

The molecular regulations of cardiac maturation are distinct from the gene regulatory network implicated in embryonic stages of cardiac development. RNA alternative splicing and the resulting isoform switching events are significant part of the post-transcriptional reprogramming during the transitional stage of maturation, driving functional refinement through a network of RNA-binding proteins.

Cardiomyocytes undergo significant changes in structure, physiology, metabolic activity, and proliferative capacities during fetal to adult maturation. Recent findings highlight the importance of post-transcriptional regulation in this process, in particular RNA alternative splicing and isoform switch. Understanding the post-transcriptional regulatory mechanisms, including key molecular players that contribute to the fetal-to-adult transition, can provide a new conceptual framework for cardiac development, diseases, and regenerative medicine.