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

Monika Piwecka(Max Delbrück Center), Petar Glažar(Max Delbrück Center), Luis R. Hernández-Miranda(Max Delbrück Center), Sebastian Memczak(Max Delbrück Center), Susanne A. Wolf(Max Delbrück Center), Agnieszka Rybak‐Wolf(Max Delbrück Center), Andrei Filipchyk(Max Delbrück Center), Filippos Klironomos(Max Delbrück Center), C Cerda(Max Delbrück Center), Pascal Fenske(Charité - Universitätsmedizin Berlin), Thorsten Trimbuch(Charité - Universitätsmedizin Berlin), Vera Zywitza(Max Delbrück Center), Mireya Plass(Max Delbrück Center), Luisa Schreyer(Max Delbrück Center), Salah Ayoub(Max Delbrück Center), Christine Kocks(Max Delbrück Center), Ralf Kühn(Max Delbrück Center), Christian Rosenmund(Charité - Universitätsmedizin Berlin), Carmen Birchmeier(Max Delbrück Center), Nikolaus Rajewsky(Max Delbrück Center)
Science
August 10, 2017
10.1126/science.aam8526
Cited by 1,263

Abstract

Cutting out circular RNAs Circular RNAs are widespread, but their functions have been controversial. Piwecka et al. used CRISPR-Cas9 technology to remove the locus encoding the circular RNA Cdr1as from the mouse genome. Single-cell electrophysiological measurements in excitatory neurons revealed an increase in spontaneous vesicle release from the knockout mice and depression in the synaptic response with two consecutive stimuli, indicating that Cdr1as deficiency leads to dysfunction of excitatory synaptic transmission. Small RNA sequencing of several major regions of the brain showed that expression of two microRNAs, miR-7 and miR-671, that bind to Cdr1as decreased and increased, respectively. These results, along with expression analyses, suggest that neuronal Cdr1as stabilizes or transports miR-7, which in turn represses genes that are early responders to different stimuli. Science , this issue p. eaam8526

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