par Penning, Audrey 
;Wang, Kun;Célérier, Margot ;Collignon, Evelyne ;Primac, Irina ;Van Der Linden, Louis ;Bizet, Martin ;Calonne, Emilie ;Hassabi, Bouchra ;Hubert, Céline ;Putmans, Pascale ;Murisier, Frédéric ;Larbanoix, Lionel ;Achouri, Younes ;Lan, Jie ;Nemazanyy, Ivan;Laurent, Sophie ;Jacquemin, Patrick;Yi, Chengqi;Deplus, Rachel ;Fuks, François
Référence bioRxiv : the preprint server for biology
Publication Publié, 2025-01-16
;Wang, Kun;Célérier, Margot ;Collignon, Evelyne ;Primac, Irina ;Van Der Linden, Louis ;Bizet, Martin ;Calonne, Emilie ;Hassabi, Bouchra ;Hubert, Céline ;Putmans, Pascale ;Murisier, Frédéric ;Larbanoix, Lionel ;Achouri, Younes ;Lan, Jie ;Nemazanyy, Ivan;Laurent, Sophie ;Jacquemin, Patrick;Yi, Chengqi;Deplus, Rachel ;Fuks, François Référence bioRxiv : the preprint server for biology
Publication Publié, 2025-01-16
Article révisé par les pairs
| Résumé : | Mitochondrial mRNA modifications are suggested to play a role in fine-tuning mitochondrial gene expression and function. However, the epitranscriptomic landscape of mitochondrial mRNA (mt-mRNA) remains poorly explored. Here, we uncover N3-methylcytosine (m3C) as a novel mt-mRNA that is catalyzed by METTL8, an enzyme previously known to modify mt-tRNA. Transcriptome-wide mapping reveals that METTL8-dependent m3C is enriched in mt-mRNAs encoding complex I subunits of the respiratory chain. Additionally, METTL8 is highly expressed in various cancers, notably in cervical cancer. METTL8 depletion impairs cell migration in vitro and reduces tumor growth in mouse xenografts. Finally, transcriptomic analyses further link METTL8 expression to oncogenic pathways, mitochondrial functions and complex I activity. Together, our results reveal a novel mitochondrial mRNA modification that promotes cancer progression.Competing Interest StatementF.F. is a co-founder of Epics Therapeutics (Gosselies, Belgium). |
