MicroRNA-126 in Atherosclerosis

MicroRNAs (miRs) are small noncoding RNAs that post-transcriptionally control gene expression by binding to target mRNAs and thereby inducing translational inhibition or mRNA degradation. Most primary miRs are endogenously processed by endonucleases such as Drosha, and the resulting pre-miRs are then cleaved by an enzyme called Dicer to form ≈22-nucleotide duplexes. One strand of the duplex, the guide strand, is preferentially selected for entry in the silencing complex by argonaute-2, whereas the other strand, known as passenger strand or miRNA* strand, is typically degraded. However, in many cases, both strands are biologically active as miRs. In that case, both distinct mature miRs arise from the same pre-miR and are referred to as 5p and 3p (Figure).Figure. Shear stress induces microRNA (miR)-126-5p, which provides atheroprotection via the inhibition of Delta-like 1 homolog (Dlk1). After processing by Dicer, miR-126-5p and miR-126-3p are loaded into RNA-induced silencing complexes. Through a mechanism yet unknown, specifically miR-126-5p levels are induced after cells are exposed to laminar shear stress. miR-126-5p inhibits the expression of Dlk1, an antiproliferative inhibitor of Notch, leading to enhanced endothelial proliferation and atheroprotection. VCAM 1 indicates vascular cell adhesion molecule 1.Several miRs control the function of …