miRNAs in endothelial cell signaling: the endomiRNAs

Abstract

microRNAs (miRNAs) have a pivotal role during the formation and function of the cardiovascular system. More than 300 miRNAs have been currently found within the mammalian genome, however only few specific miRNAs, named endomiRNAs, showed conseved endothelial cell expression and function. In this review we present an overview of the currently known endomiRNAs, focusing on their genome localization, processing and target gene repression during vasculogenesis and angiogenesis.

Figure 1. miRNAs processing and regulation

miRNA precursors (pri-miRNA) are processed by DROSHA and DGCR8 proteins into smaller RNA hairpins named pre-miRNAs. Protein-protein or RNA binding proteins are able to inhibit (Red) or promote (Green) pri-in to pre-miRNA processing with the nucleus. After export to the cytoplasm, pre-miRNAs are associated with the endo nuclease DICER and other regulatory protein such as TRBP. DICER cleaves the pre-miRNAs in a ~22 nt duplex miRNA which is incorporated in the RNA-Inducing–Silencing–Complex (RISC) where the mature miRNA associates with AGO2 to induce translation repression of the target mRNA. This process can be regulated by several growth factor singling pathways through ERK-MAP kinase or SMAD activation. hnRNP= heterogeneous nuclear riboprotein; KSRP= KH-type splicing regulatory protein; SMAD=mothers against decapentaplegic homolog; ADAR=adenosine deamenases acting in RNA.

Figure 2. Schematic representation of the endomiRNAs and their targets

Four different microRNAs families have been implicated in controlling endothelial cell behavior and signaling. Endothelial microRNAs –endomiRNAs-include miR-126 and miR-23-27-24, miR-17-92 and miR-222-221 clusters. These families of microRNAs have been found to be expressed in endothelial cells (or cells that interact with the endothelium) and thus regulate endothelial cell responses. See text for detailed information.