Circular RNAs are a large class of animal RNAs with regulatory potency

Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences. Biochemical, functional and computational analyses are combined to show that circular RNAs are a large class of animal RNAs with regulatory potency. How circRNAs round-up miRNAs Circular RNAs (circRNAs) have been detected in animal cells, but their function has been unclear. Two papers, from the laboratories of Nikolaus Rajewsky and Jørgen Kjems, have now defined a function for one circRNA that binds the microRNA miR-7. They find that this circRNA is replete with microRNA binding sites and can act as a 'sponge' capable of binding scores of miRNAs per circRNA molecule. These studies suggest a role for circRNAs in post-transcriptional regulation.