Fiche publication


Date publication

avril 2025

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David


Tous les auteurs :
Dumas L, Shin S, Rigaud Q, Cargnello M, Hernández-Suárez B, Herviou P, Saint-Laurent N, Leduc M, Le Gall M, Monchaud D, Dassi E, Cammas A, Millevoi S

Résumé

Cancer cells rely on mitochondria for their bioenergetic supply and macromolecule synthesis. Central to mitochondrial function is the regulation of mitochondrial protein synthesis, which primarily depends on the cytoplasmic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing evidence that mitochondrial protein synthesis contributes to the onset and progression of cancer, and can thus offer new opportunities for cancer therapy, knowledge of the underlying molecular mechanisms remains limited. Here, we show that RNA G-quadruplexes (RG4s) regulate mitochondrial function by modulating cytoplasmic mRNA translation of nuclear-encoded mitochondrial proteins. Our data support a model whereby the RG4 folding dynamics, under the control of oncogenic signaling and modulated by small molecule ligands or RG4-binding proteins, modifies mitochondria-localized cytoplasmic protein synthesis. Ultimately, this impairs mitochondrial functions, affecting energy metabolism and consequently cancer cell proliferation.

Mots clés

G-Quadruplexes, Humans, Mitochondria, metabolism, Energy Metabolism, genetics, Protein Biosynthesis, RNA, Messenger, metabolism, Mitochondrial Proteins, genetics, Cell Line, Tumor, Cell Proliferation, RNA, Mitochondrial, Neoplasms, genetics

Référence

Nat Commun. 2025 04 7;16(1):3292