A circular twist on microRNA regulation

Abstract

Circular RNAs (circRNAs) are a novel class of RNA whose physiological function has yet to be investigated. A recent publication in Science provides the first evidence of the biological relevance of a circRNA in an in vivo model and unveils an unexpected twist on their crosstalk with miRNAs.

Figure 1

CircRNAs can function as ceRNAs thus sponging for miRNAs. Once the circRNA is destabilized through acute treatments (e.g., with siRNAs, shRNAs, ASOs or LNA GapmeRs), the attached miRNAs are released and free to bind and repress ceRNA targets. As a final result of an acute intervention, ceRNAs are down-regulated. In a different scenario, the prolonged absence of a sponge circRNA, due to chronic treatments or knockout, leads to destabilization of its binding miRNAs through a post-transcriptional mechanism. As a consequence, other ceRNAs are no longer targeted and their expression increases.