An Overview of Circular RNAs

Circular RNAs (circRNAs) are a class of endogenous, covalently closed RNA molecules. Unlike linear RNAs, circRNAs are formed through noncanonical splicing, during which a downstream donor site is ligated with an upstream splice acceptor site, building a backsplice junction (BSJ), the distinguishing feature of circRNAs. The inherent feature of circRNAs is their lack of 5' cap structures and 3' poly(A) tails, which are typically found in linear RNAs. Due to their resistance to exonucleases, they exhibit increased stability compared to linear RNAs. In the past, circRNAs have been shown to be evolutionarily conserved and possess cell-type and tissue-specific expression patterns. The various important biological functions of circRNAs, including their roles as protein inhibitors (microRNA (miRNAs) sponges) and regulators of RNA-binding proteins (RBPs), have made them interesting biomolecules for the scientific community. However, due to the novelty of this research field, many obstacles are still present, arising from the lack of consensus on the precise methodological standards for reliable identification and nomenclature of newly identified circRNAs, inherent limitations of the applied methodologies, and the open questions regarding the mechanisms of action of this class of RNAs. This chapter will provide a brief summary of the discovery of circRNAs and the early related research. We will outline the importance of RNA sequencing technologies in circRNA research and highlight the more recent findings in this field, with a special focus on the different functions of circRNAs. Finally, we will discuss key challenges associated with circRNA research.