Circular RNAs: A Novel Class of Functional RNA Molecules with a Therapeutic Perspective

Circular RNAs (circRNAs) are a subclass of non-coding RNAs that lack free 3' and 5' ends and, thus, exist as continuous loop RNAs. Such circular transcripts have been identified for thousands of genes, are regulated in developmental stages and pathophysiological conditions, and are often expressed in a tissue- or cell-type-specific manner. For a long time, circular transcripts were considered as aberrant splicing by-products. However, high-throughput transcriptome sequencing and focused molecular characterization of individual circRNAs uncovered their ubiquity. Evidence emerges suggesting circRNAs are functional molecules. In this review, we illustrate the current knowledge of circRNA formation and circRNA detection methods. We summarize different molecular mechanisms of action and highlight circRNAs with specific roles in cardiovascular disease. Finally, we describe a number of tools for circRNA manipulation, which may be exploited for circRNA-based therapeutic interventions in the future.