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@ARTICLE{Giusti:269775,
author = {Giusti, Sebastian A and Pino, Natalia S and Pannunzio,
Camila and Ogando, Mora B and Armando, Natalia G and
Garrett, Lillian and Zimprich, Annemarie and Becker, Lore
and Gimeno, Maria L and Lukin, Jeronimo and Merino,
Florencia L and Pardi, M Belen and Pedroncini, Olivia and Di
Mauro, Giuliana C and Durner, Valerie Gailus and Fuchs,
Helmut and de Angelis, Martin Hrabě and Patop, Ines L and
Turck, Christoph W and Deussing, Jan M and Vogt Weisenhorn,
Daniela M and Jahn, Olaf and Kadener, Sebastian and Hölter,
Sabine M and Brose, Nils and Giesert, Florian and Wurst,
Wolfgang and Marin-Burgin, Antonia and Refojo, Damian},
title = {{A} brain-enriched circular {RNA} controls excitatory
neurotransmission and restricts sensitivity to aversive
stimuli.},
journal = {Science advances},
volume = {10},
number = {21},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DZNE-2024-00617},
pages = {eadj8769},
year = {2024},
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.},
keywords = {RNA, Circular: genetics / Animals / Synaptic Transmission /
Mice / Brain: metabolism / Brain: physiology / Mice,
Knockout / Neurons: metabolism / Neurons: physiology / RNA,
Circular (NLM Chemicals)},
cin = {AG Wurst},
ddc = {500},
cid = {I:(DE-2719)1140001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38787942},
pmc = {pmc:PMC11122670},
doi = {10.1126/sciadv.adj8769},
url = {https://pub.dzne.de/record/269775},
}