RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism
Abstract 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 pr...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58118-5 |
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| author | Leïla Dumas Sauyeun Shin Quentin Rigaud Marie Cargnello Beatriz Hernández-Suárez Pauline Herviou Nathalie Saint-Laurent Marjorie Leduc Morgane Le Gall David Monchaud Erik Dassi Anne Cammas Stefania Millevoi |
| author_facet | Leïla Dumas Sauyeun Shin Quentin Rigaud Marie Cargnello Beatriz Hernández-Suárez Pauline Herviou Nathalie Saint-Laurent Marjorie Leduc Morgane Le Gall David Monchaud Erik Dassi Anne Cammas Stefania Millevoi |
| author_sort | Leïla Dumas |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a2996d78a2ac47da93bcfc4632a208c2 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a2996d78a2ac47da93bcfc4632a208c22025-08-20T03:06:57ZengNature PortfolioNature Communications2041-17232025-04-0116112210.1038/s41467-025-58118-5RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolismLeïla Dumas0Sauyeun Shin1Quentin Rigaud2Marie Cargnello3Beatriz Hernández-Suárez4Pauline Herviou5Nathalie Saint-Laurent6Marjorie Leduc7Morgane Le Gall8David Monchaud9Erik Dassi10Anne Cammas11Stefania Millevoi12Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierProteom’IC facility, Université Paris Cité, CNRS, INSERM Institut CochinProteom’IC facility, Université Paris Cité, CNRS, INSERM Institut CochinInstitut de Chimie Moléculaire (ICMUB), UBFC Dijon CNRS UMR6302Laboratory of RNA Regulatory Networks, Department of Cellular, Computational and Integrative Biology (CIBIO), University of TrentoCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Equipe Labellisée Fondation ARC, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul SabatierAbstract 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.https://doi.org/10.1038/s41467-025-58118-5 |
| spellingShingle | Leïla Dumas Sauyeun Shin Quentin Rigaud Marie Cargnello Beatriz Hernández-Suárez Pauline Herviou Nathalie Saint-Laurent Marjorie Leduc Morgane Le Gall David Monchaud Erik Dassi Anne Cammas Stefania Millevoi RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism Nature Communications |
| title | RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism |
| title_full | RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism |
| title_fullStr | RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism |
| title_full_unstemmed | RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism |
| title_short | RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism |
| title_sort | rna g quadruplexes control mitochondria localized mrna translation and energy metabolism |
| url | https://doi.org/10.1038/s41467-025-58118-5 |
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