Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Federica A Falconio
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; Department of Life Sciences Imperial College London South Kensington campus, London, United Kingdom
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; IBPM CNR c/o Department of Biology and Biotechnology, Sapienza University of Rome, Rome, Italy
European Molecular Biology Laboratory (EMBL) Epigenetics & Neurobiology Unit, Campus Adriano Buzzati-Traverso, Monterotond, Italy
Benedetta Zuliani
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
Federica Mosti
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; Department of Neurobiology, Duke University Medical Center, Durham, United States
Alessandro Fatica
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
Zaira Ianniello
Department of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy
Rosa Bordone
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Alberto Macone
Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy
Enzo Agostinelli
Department of Sensory Organs, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy; International Polyamines Foundation ‘ETS-ONLUS’, Rome, Italy
Alessia Perna
Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, University Cattolica del S. Cuore, Roma, Italy
Tanja Matkovic
Freie Universität Berlin, Institute for Biology and Genetics, Berlin, Germany
Freie Universität Berlin, Institute for Biology and Genetics, Berlin, Germany
Gabriella Silvestri
Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, University Cattolica del S. Cuore, Roma, Italy; Department of Scienze dell’Invecchiamento, Neurologiche, Ortopediche e della testa-Collo; UOC Neurologia, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy; International Polyamines Foundation ‘ETS-ONLUS’, Rome, Italy; Pasteur Institute, Fondazione Cenci-Bolognetti, Rome, Italy
Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions.
