Temporal co-regulation of microRNA arms among cell types after myocardial infarction [RNA-Seq]

Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. MicroRNAs (miRNAs) shape the transcript repertoire and control cellular functions. Imprecise cleavage of miRNA hairpins during biogenesis and downstream enzymatic processing alters mature miRNA arm abundance. Using small and total RNA sequencing, miRNA temporal dynamics and regulatory effects were studied in four cell types of the heart upon myocardial infarction. We define differentially processed miRNAs, which have changes in their arm ratios and have effects on target gene regulation. The identified miRNA subsets are enriched in templated isomiR modifications and show associations with RNA binding proteins, biogenesis and other processing factors. Our analysis reveals antagonistic functions co-regulated by the processed miRNA arms, beyond known pathways involved in cardiac regeneration. This study highlights novel insights into disease mechanisms controlled by dysregulated microRNA processing concerning acute damage response as well as long-time adaptation after AMI.