Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function
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 conser...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/69269 |
| id |
doaj-e2297eac8cb54bc882d8e8ccac2b6c5b |
|---|---|
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Sonia Coni Federica A Falconio Marta Marzullo Marzia Munafò Benedetta Zuliani Federica Mosti Alessandro Fatica Zaira Ianniello Rosa Bordone Alberto Macone Enzo Agostinelli Alessia Perna Tanja Matkovic Stephan Sigrist Gabriella Silvestri Gianluca Canettieri Laura Ciapponi |
| spellingShingle |
Sonia Coni Federica A Falconio Marta Marzullo Marzia Munafò Benedetta Zuliani Federica Mosti Alessandro Fatica Zaira Ianniello Rosa Bordone Alberto Macone Enzo Agostinelli Alessia Perna Tanja Matkovic Stephan Sigrist Gabriella Silvestri Gianluca Canettieri Laura Ciapponi Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function eLife CNBP myotonic dystrophy 2 polyamine translation ODC Drosophila melanogaster |
| author_facet |
Sonia Coni Federica A Falconio Marta Marzullo Marzia Munafò Benedetta Zuliani Federica Mosti Alessandro Fatica Zaira Ianniello Rosa Bordone Alberto Macone Enzo Agostinelli Alessia Perna Tanja Matkovic Stephan Sigrist Gabriella Silvestri Gianluca Canettieri Laura Ciapponi |
| author_sort |
Sonia Coni |
| title |
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function |
| title_short |
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function |
| title_full |
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function |
| title_fullStr |
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function |
| title_full_unstemmed |
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function |
| title_sort |
translational control of polyamine metabolism by cnbp is required for drosophila locomotor function |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2021-09-01 |
| description |
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. |
| topic |
CNBP myotonic dystrophy 2 polyamine translation ODC Drosophila melanogaster |
| url |
https://elifesciences.org/articles/69269 |
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doaj-e2297eac8cb54bc882d8e8ccac2b6c5b2021-09-14T07:00:37ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.69269Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor functionSonia Coni0https://orcid.org/0000-0002-0295-8904Federica A Falconio1Marta Marzullo2https://orcid.org/0000-0001-7229-1693Marzia Munafò3https://orcid.org/0000-0002-2689-8432Benedetta Zuliani4Federica Mosti5Alessandro Fatica6Zaira Ianniello7Rosa Bordone8Alberto Macone9Enzo Agostinelli10Alessia Perna11Tanja Matkovic12Stephan Sigrist13https://orcid.org/0000-0002-1698-5815Gabriella Silvestri14Gianluca Canettieri15https://orcid.org/0000-0001-6694-2613Laura Ciapponi16https://orcid.org/0000-0002-0817-1862Department of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; Department of Life Sciences Imperial College London South Kensington campus, London, United KingdomDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; IBPM CNR c/o Department of Biology and Biotechnology, Sapienza University of Rome, Rome, ItalyEuropean Molecular Biology Laboratory (EMBL) Epigenetics & Neurobiology Unit, Campus Adriano Buzzati-Traverso, Monterotond, ItalyDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, ItalyDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, Italy; Department of Neurobiology, Duke University Medical Center, Durham, United StatesDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, ItalyDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Sensory Organs, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy; International Polyamines Foundation ‘ETS-ONLUS’, Rome, ItalyDepartment of Neuroscience, Fondazione Policlinico Gemelli IRCCS, University Cattolica del S. Cuore, Roma, ItalyFreie Universität Berlin, Institute for Biology and Genetics, Berlin, GermanyFreie Universität Berlin, Institute for Biology and Genetics, Berlin, GermanyDepartment 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, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy; International Polyamines Foundation ‘ETS-ONLUS’, Rome, Italy; Pasteur Institute, Fondazione Cenci-Bolognetti, Rome, ItalyDepartment of Biology and Biotechnologies, Sapienza University of Rome, Rome, ItalyMicrosatellite 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.https://elifesciences.org/articles/69269CNBPmyotonic dystrophy 2polyaminetranslationODCDrosophila melanogaster |