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

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Item Type:	Article
Title:	Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
Creators Name:	Piwecka, M., Glažar, P., Hernandez-Miranda, L.R., Memczak, S., Wolf, S.A., Rybak-Wolf, A., Filipchyk, A., Klironomos, F., Cerda Jara, C.A., Fenske, P., Trimbuch, T., Zywitza, V., Plass, M., Schreyer, L., Ayoub, S., Kocks, C., Kühn, R., Rosenmund, C., Birchmeier, C. and Rajewsky, N.
Abstract:	Hundreds of circular RNAs (circRNAs) are highly abundant in mammalian brain, with oftentimes conserved expression. Here, we show that the circRNA Cdr1as is massively bound by miR-7 and miR-671 in the human and mouse brain. 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 associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of microRNAs miR-7 and miR-671 was specifically and post-transcriptionally 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 circRNAs and miRNAs are important for normal brain function.
Keywords:	Behavior, Animal, Brain, CRISPR-Cas Systems, Genetic Loci, MicroRNAs, RNA, RNA Processing, Post-Transcriptional, RNA Stability, RNA, Long Noncoding, Up-Regulation, Animals, Mice, Mice, Knockout
Source:	Science
ISSN:	0036-8075
Publisher:	American Association for the Advancement of Science
Volume:	357
Number:	6357
Page Range:	eaam8526
Date:	22 September 2017
Official Publication:	https://doi.org/10.1126/science.aam8526
PubMed:	View item in PubMed

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