Impact of the cross-talk between circular and messenger RNAs on cell regulation

Circular RNAs (circRNA) are non-coding RNAs characterized by a closed-loop structure providing increased stability and enhancing their ability to compete with messenger RNAs (mRNA) for microRNA (miRNA) binding. An important open question is if circRNA plays a physiological role in the cells regulating critical cellular functions. We address this question with a combination of theoretical modeling and experimental analysis. Theoretically, we investigated two possible scenarios, one in which circRNAs act as sponges for miRNAs but there is no other relation between the two RNAs and the other one where circRNAs are co-generated with their corresponding mRNAs. We thus compared the results with data reporting the level of circRNAs (ZEB1, CANCX, ABCC1) modulating specific miRNAs in 27 cell lines. Due to the high stability of circRNAs, we show that a miRNA mediated cross-talk between circRNA and mRNA appears for a broad range of physiological parameters. This confirms the relevance of circRNAs in cell regulation, suggesting that they could be used as biomarkers.