Cited by 1,210Circular RNAs in diseasesRNA Research and SplicingCancer-related molecular mechanisms research

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

Piwecka, Monika, Glažar, Petar, Hernandez-Miranda, Luis R., Memczak, Sebastian, Wolf, Susanne A., Rybak-Wolf, Agnieszka, Filipchyk, Andrei, Klironomos, Filippos +12 more·2017·Science

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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Crossref · 10.1126/science.aam8526

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65 of 65 references verified0 citation errors · 0 not checkable

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  • miRNAs play a key role in post-transcriptional regulation and circRNAs function as miRNA sequesters to modulate the pathogenesis and progression of various diseases.

    “It is well known that miRNAs play a key role in post-transcriptional regulation and circRNAs function as miRNA sequesters to modulate the pathogenesis and progression of various diseases.32,52”
  • CiRS-7 is abundantly expressed in the mammalian brain, where it increases the translation of the miR-7 target mRNA.

    “CiRS-7 is abundantly expressed in the mammalian brain [49,62], where it increases the translation of the miR-7 target mRNA [14,49].”
  • CDR1as-deficient mice displayed a strongly impaired sensorimotor gating deficiency in which the animals were unable to filter out unnecessary information; a similar deficiency has been associated with neuropsychiatric disorders in humans.

    “In an animal model where the CR1as locus was removed from the mouse genome, CDR1as-deficient mice displayed a strongly impaired sensorimotor gating deficiency in which the animals were unable to filter out unnecessary information.A similar deficiency has been associated with neuropsychiatric disorders in humans [49].”

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Authors
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., & Rajewsky, N.
Affiliations
  • Max Delbrück Center (DE)
  • 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.
  • NeuroCure Cluster of Excellence (DE)
Corresponding author
  • Piwecka, Monika
  • Glažar, Petar
  • Hernandez-Miranda, Luis R.
  • Rajewsky, Nikolaus
Venue
Science
Published
2017-09-22
Volume
357
Issue
6357
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2744268790
Cited by
1,210
References
65
Citations by year
2026: 42 · 2025: 104 · 2024: 117 · 2023: 116 · 2022: 157 · 2021: 205 · 2020: 188 · 2019: 148 · 2018: 111 · 2017: 18 · 2013: 1
FWCI
51.96
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (award332360, WO 1418/3-1)
  • BIH (award332231, CRG 2a TP7)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
circular RNA, CDR1as, microRNA, miR-7, excitatory synaptic transmission, synaptic depression, CRISPR/Cas9 knockout, mouse brain, neuronal excitability, small RNA
MeSH terms
RNA, Circular, Animals, Behavior, Animal, Brain, Humans, RNA, RNA Processing, Post-Transcriptional, Up-Regulation, Mice, Knockout, RNA Stability, MicroRNAs, Mice, Genetic Loci, RNA, Long Noncoding, CRISPR-Cas Systems

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