Journal Article

DZNE-2024-00617

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A brain-enriched circular RNA controls excitatory neurotransmission and restricts sensitivity to aversive stimuli.

Giusti, S. A. ; Pino, N. S. ; Pannunzio, C. ; Ogando, M. B. ; Armando, N. G. ; Garrett, L. ; Zimprich, A. ; Becker, L. ; Gimeno, M. L. ; Lukin, J. ; Merino, F. L. ; Pardi, M. B. ; Pedroncini, O. ; Di Mauro, G. C. ; Durner, V. G. ; Fuchs, H. ; de Angelis, M. H. ; Patop, I. L. ; Turck, C. W. ; Deussing, J. M. ; Vogt Weisenhorn, D. M. ; Jahn, O. ; Kadener, S. ; Hölter, S. M. ; Brose, N. ; Giesert, F. ; Wurst, W.DZNE* ; Marin-Burgin, A. ; Refojo, D.

2024
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.adj8769

Abstract: Circular RNAs (circRNAs) are a large class of noncoding RNAs. Despite the identification of thousands of circular transcripts, the biological significance of most of them remains unexplored, partly because of the lack of effective methods for generating loss-of-function animal models. In this study, we focused on circTulp4, an abundant circRNA derived from the Tulp4 gene that is enriched in the brain and synaptic compartments. By creating a circTulp4-deficient mouse model, in which we mutated the splice acceptor site responsible for generating circTulp4 without affecting the linear mRNA or protein levels, we were able to conduct a comprehensive phenotypic analysis. Our results demonstrate that circTulp4 is critical in regulating neuronal and brain physiology, modulating the strength of excitatory neurotransmission and sensitivity to aversive stimuli. This study provides evidence that circRNAs can regulate biologically relevant functions in neurons, with modulatory effects at multiple levels of the phenotype, establishing a proof of principle for the regulatory role of circRNAs in neural processes.

Keyword(s): RNA, Circular: genetics (MeSH) ; Animals (MeSH) ; Synaptic Transmission (MeSH) ; Mice (MeSH) ; Brain: metabolism (MeSH) ; Brain: physiology (MeSH) ; Mice, Knockout (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: physiology (MeSH) ; RNA, Circular

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Contributing Institute(s):

1. Genome Engineering (AG Wurst)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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