MicroRNAs in cardiovascular disease: an introduction for clinicians.
Bottom Line: Individual miRNAs have been shown to regulate the expression of multiple genes.Conversely, the expression of individual genes can be regulated by multiple miRNAs.Through this review, we provide clinicians with a brief overview of the ever-expanding world of miRNAs.
Affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.Show MeSH
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Mentions: A basic schematic of how miRNAs are transcribed from the genome and processed into ≈22-mer mature (active) miRNAs is shown in figure 1. Mature miRNAs enter the RNA-induced silencing complex (RISC) by associating with Argonaute proteins. The targeting of the RISC to specific messenger RNA(s) is achieved by binding of the miRNA within the RISC to complementary sequences in the 3′ untranslated region (UTR) of target messenger RNA (mRNA). Once bound, the RISC is able to induce post-transcriptional gene silencing, through translational inhibition and/or mRNA degradation (figure 2), leading to the miRNA-mediated downregulation of the corresponding target protein.1w3–w5 The exact mechanisms by which targeting and silencing occur remain incompletely understood, although it is clear perfect complementarity across all 22 nucleotides is not required; indeed such a situation occurs rarely, if ever, in humans. It is also well recognised that pairing in the ‘seed’ region of the miRNA (nucleotides 2–7 or 8) appears most important for targeting mRNAs.w11 w12 Several software tools that predict which mRNAs may be targets for each miRNA sequence have been developed, including TargetScan (http://www.targetscan.org) and miRanda (http://www.microRNA.org). Experimentally validated targets have also been catalogued in TarBase (http://www.microrna.gr/tarbase).
Affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.