ABSTRACT
Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation of toxic RNA and have been associated to 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 age-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 muscle 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.
GRAPHICAL ABSTRACTCNBP controls muscle function by regulating the polyamine metabolism
Lack of dCNBP impairs locomotor function through ODC-polyamine downregulation
dCNBP binds dOdc mRNA and regulates its translation
Polyamine supplementation or dOdc1 reconstitution rescues locomotor defects
CNBP-ODC-polyamine levels are reduced in muscle of DM2 patients
Competing Interest Statement
The authors have declared no competing interest.