RRC ID 70795
Author Coni S, Falconio FA, Marzullo M, Munafò M, Zuliani B, Mosti F, Fatica A, Ianniello Z, Bordone R, Macone A, Agostinelli E, Perna A, Matkovic T, Sigrist S, Silvestri G, Canettieri G, Ciapponi L.
Title Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function.
Journal Elife
Abstract 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.
Volume 10
Published 2021-9-14
DOI 10.7554/eLife.69269
PII 69269
PMID 34517941
PMC PMC8439652
MeSH Animals Animals, Genetically Modified Cell Line Down-Regulation / physiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster Gene Expression Regulation / drug effects HEK293 Cells Humans Motor Activity / genetics* Motor Activity / physiology* Muscle, Skeletal / metabolism Myotonic Dystrophy / genetics Myotonic Dystrophy / metabolism Polyamines / metabolism* Protein Biosynthesis Putrescine / pharmacology RNA Interference RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Spermidine / pharmacology
IF 7.08
Drosophila DGRC#203535