Alternative polyadenylation regulation in cardiac development and cardiovascular disease

Cleavage and polyadenylation of pre-mRNAs is a necessary step for gene expression and function. Majority of human genes exhibit multiple polyadenylation sites, which can be alternatively used to generate different mRNA isoforms from a single gene. Alternative polyadenylation (APA) of pre-mRNAs is important for the proteome and transcriptome landscape. APA is tightly regulated during development and contributes to tissue-specific gene regulation. Mis-regulation of APA is linked to a wide range of pathological conditions. APA-mediated gene regulation in the heart is emerging as a new area of research. Here, we will discuss the impact of APA on gene regulation during heart development and in cardiovascular diseases. First, we will briefly review how APA impacts gene regulation and discuss molecular mechanisms that control APA. Then, we will address APA regulation during heart development and its dysregulation in cardiovascular diseases. Finally, we will discuss pre-mRNA targeting strategies to correct aberrant APA patterns of essential genes for the treatment or prevention of cardiovascular diseases. The RNA field is blooming due to advancements in RNA-based technologies. RNA-based vaccines and therapies are becoming the new line of effective and safe approaches for the treatment and prevention of human diseases. Overall, this review will be influential for understanding gene regulation at the RNA level via APA in the heart and will help design RNA-based tools for the treatment of cardiovascular diseases in the future.