Abstract
Cardiac development is an exquisitely regulated process that is sensitive to perturbations in transcriptional activity and gene dosage. Accordingly, congenital heart abnormalities are prevalent worldwide, and are estimated to occur in approximately 1% of live births. Recently, small non-coding RNAs, known as microRNAs, have emerged as critical components of the cardiogenic regulatory network, and have been shown to play numerous roles in the growth, differentiation, and morphogenesis of the developing heart. Moreover, the importance of miRNA function in cardiac development has facilitated the identification of prospective therapeutic targets for patients with congenital and acquired cardiac diseases. Here, we discuss findings attesting to the critical role of miRNAs in cardiogenesis and cardiac regeneration, and present evidence regarding the therapeutic potential of miRNAs for cardiovascular diseases.
Highlights
The survival of any metazoan during embryonic development and adult life depends on the continuous function of the heart
Cells within the first heart field, a group of myocardial progenitors originating from the anterior mesoderm, migrate from the primitive streak to the midline of the embryo where they form a crescent-shaped epithelium known as the cardiac crescent [1,7]
We present evidence regarding the therapeutic potential of miRNAs, with respect to cardiac regeneration
Summary
The survival of any metazoan during embryonic development and adult life depends on the continuous function of the heart. The lin-4 gene was unusual because it resided within an intron of another, unrelated gene [13], and encoded two small RNA molecules with complementarity to repeated sequence elements within the 3' untranslated region (3'UTR) of the protein-coding lin-14 transcript [13,14] These findings were consistent with previous reports of lin-4 functioning as a negative regulator of lin-14 during early stages of C. elegans larval development [15]. The first step of miRNA processing is the cleavage of the primary transcript into pre-miRNAs, stem-loop precursors that measure approximately 70 nucleotides in length (Figure 1) This process is mediated by the nuclear RNAse. III-like enzyme, Drosha, and its cofactor, DGCR8 The capped, poly-adenylated primary miRNA (pri-miRNA) is cleaved by the RNAse III-like enzyme, Drosha (Pasha in flies), and its partner, DGCR8, to generate a ~70 nucleotide-long pre-miRNA molecule that contains local stem-loop secondary structure. The resulting double-stranded ~22 nucleotide-long miRNA duplex consists of a “guide” and “passenger” strand; the “guide” strand is preferentially loaded into the RISC (RNA-induced silencing complex) as the mature miRNA, and guided to its target mRNA transcript
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