Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed.
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.
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Agnieszka
A
Rybak-Wolf
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Christin
C
Stottmeister
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Petar
P
Glažar
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Marvin
M
Jens
Molecular Neurobiology, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Natalia
N
Pino
Molecular Neurobiology, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Sebastian
S
Giusti
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
Mor
M
Hanan
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
Mikaela
M
Behm
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
Osnat
O
Bartok
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
Reut
R
Ashwal-Fluss
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Margareta
M
Herzog
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Luisa
L
Schreyer
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Panagiotis
P
Papavasileiou
Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Andranik
A
Ivanov
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
Marie
M
Öhman
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.
Damian
D
Refojo
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
Sebastian
S
Kadener
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.
Nikolaus
N
Rajewsky
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004331:Drosophila melanogaster; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000079962:RNA, Circular; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013569:Synapses / Q000378:metabolism
D000079962:RNA, Circular; D012333:RNA, Messenger; D012313:RNA