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miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner.
EMBO Rep. 25, 3008-3039 (2024)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
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
Journal
EMBO Reports
Quellenangaben
Volume: 25,
Issue: 7,
Pages: 3008-3039
Publisher
EMBO Press
Publishing Place
Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
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
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