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

Item Type:Article
Title:Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
Creators Name:Piwecka, M. and Glažar, P. and Hernandez-Miranda, L.R. and Memczak, S. and Wolf, S.A. and Rybak-Wolf, A. and Filipchyk, A. and Klironomos, F. and Cerda Jara, C.A. and Fenske, P. and Trimbuch, T. and Zywitza, V. and Plass, M. and Schreyer, L. and Ayoub, S. and Kocks, C. and Kühn, R. and Rosenmund, C. and 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
Publisher:American Association for the Advancement of Science
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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