Memczak, Sebastian and Jens, Marvin and Elefsinioti, Antigoni and Torti, Francesca and Krueger, Janna and Rybak, Agnieszka and Maier, Luisa and Mackowiak, Sebastian D. and Gregersen, Lea H. and Munschauer, Mathias and Loewer, Alexander and Ziebold, Ulrike and Landthaler, Markus and Kocks, Christine and Le Noble, Ferdinand and Rajewsky, Nikolaus (2013):
Circular RNAs are a large class of animal RNAs with regulatory potency.
In: Nature, 495 (7441), pp. 333-8. ISSN 1476-4687,
[Article]

Abstract

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.

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