There is much interest in how microRNAs (miRNAs), which target mRNAs to regulate gene expression, are themselves inhibited. Now, two groups have found that a naturally expressed circular RNA (circRNA) binds to miRNAs to suppress their function. Memczak et al. and Hansen et al. show that a mammalian circRNA, termed CDR1 antisense (CDR1as) or circular RNA sponge for miR-7 (ciRS-7), contains >60 conserved miR-7 seed matches, suggesting that it can bind densely to this target miRNA. miR-7 and the circRNA are co-expressed specifically in mouse neuronal tissues, which indicates that they interact endogenously. Moreover, this circRNA associates with the miRNA effector protein Argonaute, and this is miR-7-dependent. Injection of the human variant of this circRNA into zebrafish or knockdown of endogenous miR-7 result in impaired midbrain development. This, together with the finding that this circRNA affects miR-7 target gene activity, further supports a suppressive role for circRNAs. Bioinformatic data predicting the presence of thousands of circRNAs in the genome suggest that they may function as important post-transcriptional regulators.
ORIGINAL RESEARCH PAPERS
Hansen, T. B. et al. Natural RNA circles function as efficient microRNA sponges. Nature 27 Feb 2013 (doi:10.1038/nature11993)
Memczak, S. et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 27 Feb 2013 (doi:10.1038/nature11928)
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Du Toit, A. Circular RNAs as miRNA sponges. Nat Rev Mol Cell Biol 14, 195 (2013). https://doi.org/10.1038/nrm3557
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DOI: https://doi.org/10.1038/nrm3557