microRNAs in heart disease: putative novel therapeutic targets?

Abstract

microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.

Figure 1

Schematic of microRNA biogenesis and action. See text for explanation. The mature microRNA sequence is given in red. TF, transcription factor; Pol, RNA polymerase II or III; Exp5, exportin 5.

Figure 2

Schematic overview of strategies used to alter microRNA expression. (A) Cells express a microRNA profile that can become altered with disease. Antisense oligonucleotides, such as antagomirs, sponges, and erasers (in red) can capture microRNAs for knockdown or sequestrate inappropriately overexpressed microRNAs, whereas artificially introduced microRNAs (in red) can be used to overexpress microRNAs or, potentially, to replace expression of downregulated ones. These strategies have the potential to affect large numbers of different targets (for simplicity, only one target mRNA per microRNA is represented). (B) Masks and gene-specific microRNA mimics (in red) can be used to affect single targets specifically (mRNAs in different shades of blue represent a set affected by a given microRNA).