Circular RNAs (circRNAs) are emerging as a new class of non-coding RNA molecules. This unusual class of RNA species is generated by a back-splicing event of one or two exons, resulting in a covalently closed circRNA molecule. Owing to their circular form, circRNAs are protected from degradation by exonucleases and have greater stability than linear RNA. Advances in computational analysis of RNA sequencing have revealed that thousands of different circRNAs are expressed in a wide range of mammalian tissues, including the cardiovascular system. Moreover, numerous circRNAs are expressed in a disease-specific manner. A great deal of progress has been made in understanding the biogenesis and function of these circRNAs. In this Review, we discuss the current understanding of circRNA biogenesis and function, with a particular emphasis on the cardiovascular system.
Circular RNAs (circRNAs) are a large class of non-coding RNA molecules that form a covalently closed loop (unlike linear RNAs).
circRNAs are produced from precursor mRNA back-splicing, a process catalysed by the spliceosome machinery.
High-throughput sequencing has identified thousands of circRNAs in the human body, a great number of which are expressed in a tissue-specific or disease-specific manner.
Although the biological functions of most circRNAs remain unknown, specific circRNAs have been shown to act as microRNA sponges, to interact with RNA-binding proteins, to regulate transcription or to be translated into proteins.
Preliminary studies have provided evidence that individual circRNAs have critical regulatory functions in the cardiovascular system.
Owing to their high stability and abundance in bodily fluids, circRNAs have potential as useful biomarkers for various diseases, including cardiovascular disease.
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Nature Reviews Cardiology thanks G. Condorelli, C. Dieterich and the other anonymous reviewer(s) for their contribution to the peer review of this work.
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The role of circular RNA HECTD1 expression in disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke
Journal of Clinical Laboratory Analysis (2019)
Nature Reviews Cardiology (2019)
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (2019)