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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.* ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; 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. ; Marin-Burgin, A.* ; Refojo, D.*

A brain-enriched circular RNA controls excitatory neurotransmission and restricts sensitivity to aversive stimuli.

Sci. Adv. 10:eadj8769 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gene-expression; Mice; Quantification; Biogenesis; Database; Abundant; Cells; State; Seq
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 10, Heft: 21, Seiten: , Artikelnummer: eadj8769 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
G-500692-001
G-500600-001
Förderungen Volkswagen Foundation
Swiss National Science Foundation-SNSF
Max Planck Society
German Federal Ministry of Education and Research
Fondo para la Convergencia Estructural del Mercosur-FOCEM
Consejo Nacional de Investigaciones Cientificas y Tecnicas
Agencia Nacional de Promoción Científica y Tecnológica
DOI 10.1126/sciadv.adj8769
WOS ID 001263685300001
Scopus ID 85194218757
PubMed ID 38787942
Erfassungsdatum 2024-06-03
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