The Functions and Mechanisms of Translatable Circular RNAs.

Circular RNAs (circRNAs) are covalently closed RNA produced by back-splicing. CircRNAs have been considered as a type of noncoding 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 physiologic and pathologic 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 the translation of circRNA could facilitate the identification of novel drug targets in various diseases. Moreover, some circRNA encoded proteins were demonstrated to have therapeutic functions in cancer. The application of synthetic circRNAs as carriers to achieve stable protein expression in vitro and in vivo has tremendous therapeutic potential.