Circular RNAs Fifty Years After Their Discovery

Circular RNAs (circRNAs) are a unique class of covalently closed molecules formed through non-canonical splicing and characterized by a markedly greater stability compared to linear RNAs. Although the first circRNA was discovered half a century ago in 1976 in a viroid, they had remained largely overlooked for several decades. Over the past ten years, the however, interest in circRNAs has grown substantially, even as their biological functions and overall significance continue to be debated. It is now well established that circRNAs constitute a large and diverse group of molecules with varied origins and properties. They have been identified across a wide range of organisms, from prokaryotes to plants and mammals, where they participate in the regulation of numerous cellular processes. The unique properties of circRNAs are beginning to be exploited for practical applications, including their use as disease biomarkers and platforms for the development of novel therapeutic strategies. This review summarizes the knowledge accumulated on circRNAs since their discovery and highlights recent advances in understanding their biology and potential applications.