A Hearty Dose of Noncoding RNAs: The Imprinted DLK1-DIO3 Locus in Cardiac Development and Disease

The imprinted Dlk1-Dio3 genomic region harbors a noncoding RNA cluster encoding over fifty microRNAs (miRNAs), three long noncoding RNAs (lncRNAs), and a small nucleolar RNA (snoRNA) gene array. These distinct noncoding RNAs (ncRNAs) are thought to arise from a single polycistronic transcript that is subsequently processed into individual ncRNAs, each with important roles in diverse cellular contexts. Considering these ncRNAs are derived from a polycistron, it is possible that some coordinately regulate discrete biological processes in the heart. Here, we provide a comprehensive summary of Dlk1-Dio3 miRNAs and lncRNAs, as they are currently understood in the cellular and organ-level context of the cardiovascular system. Highlighted are expression profiles, mechanistic contributions, and functional roles of these ncRNAs in heart development and disease. Notably, a number of these ncRNAs are implicated in processes often perturbed in heart disease, including proliferation, differentiation, cell death, and fibrosis. However, most literature falls short of characterizing precise mechanisms for many of these ncRNAs, warranting further investigation. Taken together, the Dlk1-Dio3 locus represents a largely unexplored noncoding regulator of cardiac homeostasis, harboring numerous ncRNAs that may serve as therapeutic targets for cardiovascular disease.