Cardioprotective microRNAs

Abstract

MicroRNAs (miRNAs) are involved in almost every aspect of a mammalian cell's functionality, from stem cell differentiation to aging and pathogenesis; however, their role in immediate cell signaling is less defined. This has been recently demonstrated by the rapid increase or decrease of miR-21's abundance within minutes of activation or inhibition of the v-akt murine thymoma viral oncogene homolog 1 (AKT) pathway, respectively, which mediates its regulation of Fas ligand and phosphatase and tensin homologue deleted on chromosome 10 expression, among other targets. Conversely, AKT induces rapid downregulation of miR-199a-5p to effect upregulation of hypoxia-inducible factor 1α and sirtuin 1. This suggests that posttranscriptional mechanisms regulate miRNAs' processing and/or stability to induce the rapid fluctuation in their levels. In support, a growing number of studies are showing specific posttranscriptional regulation of miRNAs. The data potentially explain how AKT, and plausibly other signaling pathways, can specifically and promptly modulate a gene's translation while circumventing the need for transcription during transient signaling events.