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Georgii, E. ; Woehler, A.* ; Piwecka, M.* ; Rajewsky, N.*

miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner.

EMBO Rep. 25, 3008-3039 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The circular RNA (circRNA) Cdr1as is conserved across mammals and highly expressed in neurons, where it directly interacts with microRNA miR-7. However, the biological function of this interaction is unknown. Here, using primary cortical murine neurons, we demonstrate that stimulating neurons by sustained depolarization rapidly induces two-fold transcriptional upregulation of Cdr1as and strong post-transcriptional stabilization of miR-7. Cdr1as loss causes doubling of glutamate release from stimulated synapses and increased frequency and duration of local neuronal bursts. Moreover, the periodicity of neuronal networks increases, and synchronicity is impaired. Strikingly, these effects are reverted by sustained expression of miR-7, which also clears Cdr1as molecules from neuronal projections. Consistently, without Cdr1as, transcriptomic changes caused by miR-7 overexpression are stronger (including miR-7-targets downregulation) and enriched in secretion/synaptic plasticity pathways. Altogether, our results suggest that in cortical neurons Cdr1as buffers miR-7 activity to control glutamatergic excitatory transmission and neuronal connectivity important for long-lasting synaptic adaptations.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cdr1as ; Neuronal Activity ; Circrna ; Mir-7 ; Mirna; Immediate-early Genes; Circular Rnas; Messenger-rna; Expression; Micrornas; Release; Growth; Cells; Fos; Jun
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Zeitschrift EMBO Reports
Quellenangaben Band: 25, Heft: 7, Seiten: 3008-3039 Artikelnummer: , Supplement: ,
Verlag EMBO Press
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Förderungen National Science Centre
DFG Leibniz Award
DFG Neurocure/BrianBank
MDC graduate program
DZHK project
EU ITN-circular RNA Biology Training Network: circRTrain
DFG Excellence Cluster
Helmholtz Association's Initiative and Networking Fund through Helmholtz AI
Polish National Agency for Academic Exchange
Projekt DEAL