Coding potential of circRNAs: new discoveries 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. This discovery is no accident. In the last century, scientist detected the ability of translate in some virus and artificial circRNAs. Artificial circRNA translation products are usually nonfunctional, whereas natural circRNA translation products are completely different. Those new proteins have various functions, which greatly broadens the new ideas and research direction for our research. These series findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we summarize the evidence concerning translation potential of circRNAs, including synthetic and endogenous circRNA translation ability, and discuss the mechanisms of circRNA translation.