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Mol Cell. 2015 Jun 4;58(5):870-85. doi: 10.1016/j.molcel.2015.03.027. Epub 2015 Apr 23.

Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed.

Author information

1
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
2
Molecular Neurobiology, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
3
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
4
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
5
Molecular Neurobiology, Max Planck Institute of Psychiatry, 80804 Munich, Germany; Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET - Partner Institute of the Max Planck Society, C1425FQD Buenos Aires, Argentina.
6
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: rajewsky@mdc-berlin.de.

Abstract

Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers.

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PMID:
25921068
DOI:
10.1016/j.molcel.2015.03.027
[Indexed for MEDLINE]
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