Impact of miR-1/miR-133 Cluster in Cardiogenesis and Heart Failure

Cardiogenesis begins during gastrulation with the bilateral specification of precardiac mesoderm on either side of the embryo. These fields fuse at the embryonic midline to form the linear heart tube, which subsequently undergoes rightward looping and chamber formation. Expansion and septation of the primitive atrial and ventricular chambers establish separate systemic and pulmonary circuits with correctly aligned inflow and outflow tracts. These morphogenetic events depend on the coordinated activation and repression of cell type-specific cardiac gene programmes controlled at transcriptional and post-transcriptional levels by cardiac transcription factors and paracrine/autocrine signals. Non-coding RNAs, particularly microRNAs and long non-coding RNAs, add an essential regulatory layer. MicroRNAs are endogenous ≈22-nt RNAs that modulate gene expression predominantly at the post-transcriptional level. The muscle-enriched miR-1/miR-133 cluster is essential for normal cardiogenesis, whereas dysregulation of miR-1 and miR-133 contributes to heart failure and its associated pathological processes. Here, we provide a state-of-the-art review of the genomic regulation, developmental functions, context-dependent interactions, and translational potential of the miR-1/miR-133 cluster in cardiogenesis and heart failure.