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Science. 2017 Sep 22;357(6357). pii: eaam8526. doi: 10.1126/science.aam8526. Epub 2017 Aug 10.

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

Author information

1
Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
2
Laboratory for Developmental Biology and Signal Transduction, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
3
Experimental and Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
4
Laboratory for Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
5
Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany.
6
Transgenic Core Facility, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
7
Berlin Institute of Health, Kapelle-Ufer 2, Berlin, Germany.
8
Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany. rajewsky@mdc-berlin.de.

Abstract

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos, a direct miR-7 target, was enhanced in Cdr1as-deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function.

Comment in

PMID:
28798046
DOI:
10.1126/science.aam8526
[Indexed for MEDLINE]

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