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

  • Monika Piwecka
    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.
  • Petar Glažar
    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.
  • Luis R. Hernandez-Miranda
    Laboratory for Developmental Biology and Signal Transduction, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
  • Sebastian Memczak
    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.
  • Susanne A. Wolf
    Laboratory for Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
  • Agnieszka Rybak-Wolf
    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.
  • Andrei Filipchyk
    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.
  • Filippos Klironomos
    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.
  • Cledi Alicia Cerda Jara
    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.
  • Pascal Fenske
    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany.
  • Thorsten Trimbuch
    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany.
  • Vera Zywitza
    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.
  • Mireya Plass
    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.
  • Luisa Schreyer
    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.
  • Salah Ayoub
    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.
  • Christine Kocks
    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.
  • Ralf Kühn
    Transgenic Core Facility, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
  • Christian Rosenmund
    Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany.
  • Carmen Birchmeier
    Laboratory for Developmental Biology and Signal Transduction, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, Berlin-Buch, Germany.
  • Nikolaus Rajewsky
    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.

書誌事項

公開日
2017-09-22
DOI
  • 10.1126/science.aam8526
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:title>Cutting out circular RNAs</jats:title> <jats:p> Circular RNAs are widespread, but their functions have been controversial. Piwecka <jats:italic>et al.</jats:italic> 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. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6357" page="eaam8526" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aam8526">eaam8526</jats:related-article> </jats:p>

収録刊行物

  • Science

    Science 357 (6357), eaam8526-, 2017-09-22

    American Association for the Advancement of Science (AAAS)

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