Fiche publication
Date publication
février 2020
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David
Tous les auteurs :
Moruno-Manchon JF, Lejault P, Wang Y, McCauley B, Honarpisheh P, Morales Scheihing DA, Singh S, Dang W, Kim N, Urayama A, Zhu L, Monchaud D, McCullough LD, Tsvetkov AS
Lien Pubmed
Résumé
Guanine-rich DNA sequences can fold into four-stranded G-quadruplex (G4-DNA) structures. G4-DNA regulates replication and transcription, at least in cancer cells. Here, we demonstrate that, in neurons, pharmacologically stabilizing G4-DNA with G4 ligands strongly downregulates the gene. is a critical gene for the initiation of autophagy that exhibits decreased transcription with aging. Using an in vitro assay, we show that a putative G-quadruplex-forming sequence (PQFS) in the first intron of the gene folds into a G4. An antibody specific to G4-DNA and the G4-DNA-binding protein PC4 bind to the PQFS. Mice treated with a G4 stabilizer develop memory deficits. Brain samples from aged mice contain G4-DNA structures that are absent in brain samples from young mice. Overexpressing the G4-DNA helicase Pif1 in neurons exposed to the G4 stabilizer improves phenotypes associated with G4-DNA stabilization. Our findings indicate that G4-DNA is a novel pathway for regulating autophagy in neurons.
Mots clés
G-quadruplex, aging, autophagy, cell biology, mouse, neurodegeneration, neurons, neuroscience, rat
Référence
Elife. 2020 Feb 11;9:
