Abstract
Circular RNAs (circRNAs) are a class of non-coding RNA that were previously thought to be insignificant byproducts of splicing errors. However, recent advances in RNA sequencing confirmed the presence of circRNAs in multiple cell lines and across different species suggesting a functional role of this RNA species. CircRNAs arise from back-splicing events resulting in a circular RNA that is stable, specific and conserved. They can be generated from exons, exon-introns, or introns. CircRNAs have multifaceted functions. They are likely part of the competing endogenous RNA class. They can regulate gene expression by sponging microRNAs, binding proteins or they can be translated into a protein themselves. CircRNAs have been associated with health and disease, some with disease protective effects, some with disease promoting functions. The widespread expression and disease regulatory mechanisms endow circRNAs to be used as functional biomarkers and therapeutic targets for a variety of different disorders. In this concise article we provide an overview of the association of circRNAs with various diseases including cancer, cardiovascular and kidney disease as well as cellular senescence. We conclude with an assessment of the current status and future outlook of this new field of research that carries immense potential with respect to diagnostic and therapeutic approaches of a variety of diseases.
Highlights
Cellular ribonucleic acids are a family of coding and non-coding sequences
Aside from mRNA which represents 3–7% (Hastie and Bishop, 1976; Carter et al, 2005) of the total RNA species in mammalian cells, the majority of the RNA species are of the non-coding category that include ribosomal RNA (80– 90% Wolf and Schlessinger, 1977; Duncan and Hershey, 1983; Palazzo and Lee, 2015), transfer RNA (10–15%; Waldron and Lacroute, 1975; Palazzo and Lee, 2015), long non-coding RNA (0.06–0.2%; Mortazavi et al, 2008; Palazzo and Lee, 2015), microRNA (0.003–0.02%; Bissels et al, 2009; Palazzo and Lee, 2015), and circular RNA (0.002–0.03%; Salzman et al, 2012; Palazzo and Lee, 2015) among others
They are ubiquitously expressed and thousands of members have already been identified. This fact only expands their potential to possibly enhance our knowledge to understand the difference between health and disease. Owing to their structure stability and their presence in exosomes circular RNA (circRNA) may exert their function in an autocrine, paracrine and possible endocrine fashion
Summary
1–2% of the human genome is transcribed into RNA transcripts, which are translated into protein (Lorenzen and Thum, 2016; Brandenburger et al, 2018). Small RNAs including microRNAs, which lead to the repression of gene/protein expression and/or translational inhibition of protein synthesis by post-transcriptional binding of the 3 -untranslated region (UTR) of mRNA targets, have been extensively studied over the past several years (Lorenzen and Thum, 2016; Brandenburger et al, 2018).
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