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Hangover Links Nuclear RNA Signaling to cAMP Regulation via the Phosphodiesterase 4d Ortholog dunce

Authors :
Manuela Ruppert
Mirjam Franz
Anastasios Saratsis
Laura Velo Escarcena
Oliver Hendrich
Li Ming Gooi
Isabell Schwenkert
Ansgar Klebes
Henrike Scholz
Source :
Cell Reports, Vol 18, Iss 2, Pp 533-544 (2017)
Publication Year :
2017
Publisher :
Elsevier, 2017.

Abstract

Summary: 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. : Cellular stressors like ethanol cause specific behavioral changes. Ruppert et al. show that the nuclear stress RNA-interacting protein Hangover is broadly expressed but only required in neurons mediating experience-dependent changes in behavior. At the cellular level, Hangover links nuclear signaling to cAMP regulation via the phosphodiesterase 4d ortholog Dunce. Keywords: hangover, dunce, Dunce isoforms, PDE4d, cellular stress, alcohol tolerance, Drosophila melanogaster

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
18
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.5e219d7d7d148fe9824fdbdaa188207
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2016.12.048