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Published on: August 21, 2014
CNBP regulates wing development in Drosophila melanogaster by promoting IRES-dependent translation of dMyc
Laura Antonucci1, Davide D'Amico2, Laura Di Magno1
1Department of Molecular Medicine; Sapienza University; Rome, Italy; Istituto Pasteur - Fondazione Cenci Bolognetti; Rome, Italy.
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.
Insights
CCHC-type zinc finger nucleic acid binding protein (CNBP) is essential for Drosophila development. This study reveals CNBP controls wing size by regulating dMyc translation via an IRES-dependent mechanism, not mRNA levels.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- CCHC-type zinc finger nucleic acid binding protein (CNBP) is a conserved protein crucial for development and disease.
- Previous studies linked CNBP to developmental defects via c-myc mRNA regulation in animal models.
- CNBP functions as a molecular chaperone binding single-stranded nucleic acids, impacting transcription and translation.
Purpose of the Study:
- Investigate the role of CNBP in Drosophila melanogaster development.
- Elucidate the mechanism by which CNBP influences dMyc expression and its impact on development.
- Determine if CNBP regulates dMyc at the mRNA or protein level in Drosophila.
Main Methods:
- Gene ablation and knockdown experiments in Drosophila melanogaster.
- Analysis of dMyc mRNA and protein levels following CNBP manipulation.
- Investigation of IRES-dependent translation mechanisms.
- Rescue experiments by reintroducing dMyc in CNBP-deficient tissues.
Main Results:
- CNBP is essential in Drosophila, with its absence causing embryonic lethality.
- CNBP deficiency reduces dMyc protein levels without affecting dMyc mRNA.
- dCNBP regulates dMyc translation via an IRES-dependent mechanism.
- CNBP knockdown in wings reduces wing size, which is rescued by dMyc reintroduction.
Conclusions:
- CNBP controls Drosophila wing development by regulating dMyc IRES-dependent translation.
- This uncharacterized mechanism highlights a novel CNBP-Myc axis in development.
- Findings suggest potential implications for other species and disease contexts.
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