Exploiting the hypoxia sensitive non-coding genome for organ-specific physiologic reprogramming

In this review we highlight the role of non-coding RNAs in the development and progression of cardiac pathology and explore the possibility of disease-associated RNAs serving as targets for cardiac-directed therapeutics. Contextually, we focus on the role of stress-induced hypoxia as a driver of disease development and progression through activation of hypoxia inducible factor 1α (HIF1α) and explore mechanisms underlying HIFα function as an enforcer of cardiac pathology through direct transcriptional coupling with the non-coding transcriptome. In the interest of clarity, we will confine our analysis to cardiac pathology and focus on three defining features of the diseased state, namely metabolic, growth and functional reprogramming. It is the aim of this review to explore possible mechanisms through which HIF1α regulation of the non-coding transcriptome connects to spatiotemporal control of gene expression to drive establishment of the diseased state, and to propose strategies for the exploitation of these unique RNAs as targets for clinical therapy. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.