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

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

Monika Piwecka  1 , Petar Glažar  1 , Luis R Hernandez-Miranda  2 , Sebastian Memczak  1   3 , Susanne A Wolf  4 , Agnieszka Rybak-Wolf  1 , Andrei Filipchyk  1 , Filippos Klironomos  1 , Cledi Alicia Cerda Jara  1 , Pascal Fenske  5 , Thorsten Trimbuch  5 , Vera Zywitza  1 , Mireya Plass  1 , Luisa Schreyer  1 , Salah Ayoub  1 , Christine Kocks  1 , Ralf Kühn  6   7 , Christian Rosenmund  5 , Carmen Birchmeier  2 , Nikolaus Rajewsky  8
Affiliations

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

Monika Piwecka et al. Science. .

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.

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Comment in

  • Non-coding RNA: Regulatory circles.
    Yates D. Yates D. Nat Rev Neurosci. 2017 Sep 19;18(10):570-571. doi: 10.1038/nrn.2017.118. Nat Rev Neurosci. 2017. PMID: 28924259 No abstract available.
  • A circular twist on microRNA regulation.
    Bezzi M, Guarnerio J, Pandolfi PP. Bezzi M, et al. Cell Res. 2017 Dec;27(12):1401-1402. doi: 10.1038/cr.2017.136. Epub 2017 Oct 31. Cell Res. 2017. PMID: 29086764 Free PMC article.

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