title: CNBP regulates wing development in Drosophila melanogaster by promoting IRES-dependent translation of dMyc.
abstract: CCHC-type zinc finger nucleic acid binding protein (CNBP) is a small conserved protein, which plays a key role in development and disease. Studies in animal models have shown that the absence of CNBP results in severe developmental defects that have been mostly attributed to its ability to regulate c-myc mRNA expression. Functionally, CNBP binds single-stranded nucleic acids and acts as a molecular chaperone, thus regulating both transcription and translation.   In this work we report that in Drosophila melanogaster, CNBP is an essential gene, whose absence causes early embryonic lethality. In contrast to what observed in other species, ablation of CNBP does not affect dMyc mRNA expression, whereas the protein levels are markedly reduced. We demonstrate for the first time that dCNBP regulates dMyc translation through an IRES-dependent mechanism, and that knockdown of dCNBP in the wing territory causes a general reduction of wing size, in keeping with the reported role of dMyc in this region. Consistently, reintroduction of dMyc in CNBP-deficient wing imaginal discs rescues the wing size, further supporting a key role of the CNBP-Myc axis in this context. Collectively, these data show a previously uncharacterized mechanism, whereby, by regulating dMyc IRES-dependent translation, CNBP controls Drosophila wing development. These results may have relevant implications in other species and in pathophysiological conditions.
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy; Istituto Pasteur - Fondazione Cenci Bolognetti; Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Antonucci
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: D'Amico
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy; Istituto Pasteur - Fondazione Cenci Bolognetti; Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Di Magno
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti; Rome, Italy; CNRS UMR 7277; INSERM 1091; Institut de Biologie de Valrose (iBV); Université de Nice-Sophia Antipolis; Nice, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Coni
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Di Marcotullio
authors.affiliation: Cellular Biology and Neurobiology Institute; IBCN; National Research Council; Monterotondo, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cardinali
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy; Istituto Pasteur - Fondazione Cenci Bolognetti; Rome, Italy; Neuromed Institute; Pozzilli, Italy; Center for Life NanoScience at LaSapienza; Istituto Italiano di Tecnologia; Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.affiliation: Department of Biology and Biotechnologies; Sapienza University; Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ciapponi
authors.affiliation: Department of Molecular Medicine; Sapienza University; Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Canettieri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008969:Molecular Sequence Data; D011132:Polyribosomes / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development*
chemical_list: C000594458:CNBP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: CNBP; Drosophila; dMyc; development; oncogene