TY  - JOUR
AU  - Giusti, Sebastian A
AU  - Pino, Natalia S
AU  - Pannunzio, Camila
AU  - Ogando, Mora B
AU  - Armando, Natalia G
AU  - Garrett, Lillian
AU  - Zimprich, Annemarie
AU  - Becker, Lore
AU  - Gimeno, Maria L
AU  - Lukin, Jeronimo
AU  - Merino, Florencia L
AU  - Pardi, M Belen
AU  - Pedroncini, Olivia
AU  - Di Mauro, Giuliana C
AU  - Durner, Valerie Gailus
AU  - Fuchs, Helmut
AU  - de Angelis, Martin Hrabě
AU  - Patop, Ines L
AU  - Turck, Christoph W
AU  - Deussing, Jan M
AU  - Vogt Weisenhorn, Daniela M
AU  - Jahn, Olaf
AU  - Kadener, Sebastian
AU  - Hölter, Sabine M
AU  - Brose, Nils
AU  - Giesert, Florian
AU  - Wurst, Wolfgang
AU  - Marin-Burgin, Antonia
AU  - Refojo, Damian
TI  - A brain-enriched circular RNA controls excitatory neurotransmission and restricts sensitivity to aversive stimuli.
JO  - Science advances
VL  - 10
IS  - 21
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DZNE-2024-00617
SP  - eadj8769
PY  - 2024
AB  - 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.
KW  - RNA, Circular: genetics
KW  - Animals
KW  - Synaptic Transmission
KW  - Mice
KW  - Brain: metabolism
KW  - Brain: physiology
KW  - Mice, Knockout
KW  - Neurons: metabolism
KW  - Neurons: physiology
KW  - RNA, Circular (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38787942
C2  - pmc:PMC11122670
DO  - DOI:10.1126/sciadv.adj8769
UR  - https://pub.dzne.de/record/269775
ER  -