Circular RNA translation – new discovery and challenges

The circular (circ)RNAs are a newly recognized group of noncoding (nc)RNAs. Research to characterize the functional features of circRNAs has uncovered distinctive profiles of conservation, stability, specificity and complexity. However, a new line of evidence has indicated that although circRNAs can function as ncRNAs, such as in the role of miRNA sponges, they are also capable of coding proteins. To date, several circRNAs have been verified to be able to translate proteins or peptides with functions that mainly influence the functions of their maternal genes. These findings greatly broaden our research approach and the knowledge of ncRNAs, meanwhile these findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we systematically summarize the history and evidence for the translation of circRNAs, including the evolution implications, molecular structures, regulation and mechanism, experimental validation and computational prediction for the coding ability of circRNAs.