TY  - JOUR
A1  - Ruppert, Manuela
A1  - Franz, Mirjam
A1  - Saratis, Anastasios
A1  - Escarcena, Laura Velo
A1  - Hendrich, Oliver
A1  - Gooi, Li Ming
A1  - Schwenkert, Isabell
A1  - Klebes, Ansgar
A1  - Scholz, Henrike
T1  - Hangover links nuclear RNA signaling to cAMP regulation via the phosphodiesterase 4d ortholog dunce
JF  - Cell Reports
N2  - The hangover gene defines a cellular stress pathway that is required for rapid ethanol tolerance in Drosophila melanogaster. To understand how cellular stress changes neuronal function, we analyzed Hangover function on a cellular and neuronal level. We provide evidence that Hangover acts as a nuclear RNA binding protein and we identified the phosphodiesterase 4d ortholog dunce as a target RNA. We generated a transcript-specific dunce mutant that is impaired not only in ethanol tolerance but also in the cellular stress response. At the neuronal level, Dunce and Hangover are required in the same neuron pair to regulate experience-dependent motor output. Within these neurons, two cyclic AMP (cAMP)-dependent mechanisms balance the degree of tolerance. The balance is achieved by feedback regulation of Hangover and dunce transcript levels. This study provides insight into how nuclear Hangover/RNA signaling is linked to the cytoplasmic regulation of cAMP levels and results in neuronal adaptation and behavioral changes.
KW  - biology
KW  - hangover
KW  - dunce
KW  - Dunce isoforms
KW  - PDE4d
KW  - cellular stress
KW  - alcohol tolerance
KW  - Drosophila melanogaster
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171950
VL  - 18
IS  - 2
ER  -