MicroRNAs

Abstract

MicroRNAs (miRs) are small noncoding RNAs (≈23 nucleotides) that regulate gene expression at a posttranscriptional level by degradation or translational inhibition of target mRNAs. Initially discovered as regulators of development in plants, worms, and fruitflies, miRs are emerging as pivotal modulators of cardiovascular biology and disease in mice and men.1 Besides a cell-specific transcription factor profile, cell-specific miR-regulated gene expression is integral to cell fate and activation decisions. Thus, the cell types involved in atherosclerosis, vascular disease, and its myocardial sequelae may be differentially regulated by distinct miRs, thereby controlling highly complex processes, for example, smooth muscle cell phenotype and inflammatory responses of endothelial cells or macrophages.2 The generation of mature miR strands requires several steps of processing of the primary miR gene transcript, including cleavage of the terminal loop of miR-precursors by the RNase III enzyme, Dicer, to produce miR duplexes. Although either strand of the miR duplex can be stably associated with an Argonaute (Ago) family protein, preferential loading of a specific strand (ie, the guide strand) onto the miR-induced silencing complex (RISC) is common. The strand that is not loaded into the RISC (ie, the passenger strand or miR*) is typically degraded.3 Strand selection may be tissue-specific, and an accumulation observed for both strands implies that each strand can separately enter the silencing complex.4 Because of the often imperfect complementary binding of the miR seed sequence to the mRNA recognition element, an individual miR can affect the expression of hundreds of target mRNAs. However, the degree of repression seems to be …