The Functions and Mechanisms of Translatable Circular RNAs

Circular RNAs (circRNAs) are covalently closed RNA produced by back-splicing. Circ RNAs have been considered as a type of non-coding RNAs for a long time. However, recent studies have shown that circRNAs can be translated into functional proteins. Proteins specifically encoded by circRNAs have been proved to play important roles in cancer pathology. In this review, we introduce the methods commonly used to identify and validate circRNA translation in detail. We also describe the major mechanisms driving the translation of these circRNAs. In addition, we summarize the main functions of the circRNA-encoded proteins in both physiological and pathological conditions. Finally, we discuss the therapeutic potential and challenges in the usage of synthetic translatable circRNAs. This brief review highlights recent discoveries made in this field and the progress of therapy based on translatable circRNAs. Significance Statement Understanding of the translation of circRNA could facilitate identification of novel drug targets in various diseases. Moreover, some circRNA encoded proteins were proved to have therapeutic function in cancer. The application of synthetic circRNAs as carriers to achieve stable protein expression in vitro and in vivo has great therapeutic potential.