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Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
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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“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”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [32]
In the citing paper
“CiRS-7 is abundantly expressed in the mammalian brain [49,62], where it increases the translation of the miR-7 target mRNA [14,49].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [49]
In the citing paper
“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].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [49]
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Metadata
- 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
- ORCID
- Piwecka, Monika
- Glažar, Petar
- Hernandez-Miranda, Luis R.
- Memczak, Sebastian
- Wolf, Susanne A.
- Filipchyk, Andrei
- Klironomos, Filippos
- Cerda Jara, Cledi Alicia
- Fenske, Pascal
- Trimbuch, Thorsten
- Zywitza, Vera
- Plass, Mireya
- Ayoub, Salah
- Kocks, Christine
- Kühn, Ralf
- Rosenmund, Christian
- Birchmeier, Carmen
- 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
- 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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