A-to-I RNA Editing in Cardiomyocytes: Profiling the Landscape in Cell Differentiation and Ischemic Heart Disease

Abstract

The unceasing progress in sequencing technologies and analytical methods in recent years has resulted in the rise in attention to epitranscriptomics – a form of which is RNA editing, the most common form being A-to-I RNA editing. ADAR-mediated A-to-I RNA editing is well-studied in cancers but is relatively uncharted in the human heart. In this study, two datasets were analyzed for A-to-I RNA editing activity, representing cardiac differentiation and ischemic heart disease (IHD). Identification of editing sites was done through a pipeline mainly utilizing GATK’s variant calling suite as the core. A total of 35,948 and 24,797 unique editing sites were identified in the differentiation and IHD datasets, respectively, mainly affecting Alu repeats located in 3’UTR and intronic regions. LIN28A was significantly differently edited across the cardiac differentiation time course, though this might not be exclusive to cardiomyocytes. In IHD, RYR2 and FKBP5 were among the genes corresponding to the top editing sites. A-to-I RNA editing activity was also found to induce protein recoding in both datasets, corresponding to transcripts known to be edited in cancers such as SRP9, COG3, KANSL1, and COPA. The exact functional implications remain to be determined, though this study provides a baseline of the landscape of A-to-I RNA editing in cardiomyocyte differentiation and disease state.