Nature communications · 2026
Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.
СтатьяНазвание и аннотация: Перевод в очереди
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Kahi Michel, Mazzu Abigail, Batistic Ludovic, Pujalte-Martin Marc, Tiroille Victor, Vincent Anne, Murdaca Joseph, Trapani Loic, Kousteridou Paraskevi, Benaceur Oumayma, Belaid Amine, Irondelle Marie, Thomas Emilie, Boscagli Christelle, Bertrand Pierre, Carr Heather S, Larbret Frédéric, Baudelet Emilie, Audebert Stéphane, Pisani Didier F, Baron Silvère, Camoin Luc, Carlier Mathieu, Durand Matthieu, Ambrosetti Damien, Chen Yu, Diaz Jean-Jacques, Jacquel Arnaud, Ben-Sahra Issam, Mazure Nathalie M, Peraldi Pascal, Bost Frédéric
Аннотация
Protein synthesis plays a central role in cancer development and progression. eukaryotic initiation factor 5 A (eIF5A), a translation factor activated by hypusination, is implicated in tumorigenesis, however, its mode of action is still unclear. We find that hypusinated eIF5A (eIF5Ahyp) promotes metastasis and tumor growth in prostate cancer (PCa) by supporting mitochondrial metabolism and translation. eIF5Ahyp controls the subcellular localization of Mitochondrial Ribonuclease P Protein 3 (MRPP3) mRNA encoding a protein essential for mitochondrial tRNA (mt-tRNA) maturation. We show that eIF5Ahyp regulates the nuclear export of MRPP3 mRNA, its expression, thereby promoting mt-tRNA maturation. Our findings establish that MRPP3 enhances mitochondrial metabolism and supports PCa metastasis. Importantly, its expression restores mitochondrial translation and tumor growth inhibited by the downregulation of eIF5Ahyp. Together, we uncover a critical role for eIF5Ahyp in mitochondrial protein synthesis and highlight its broader implications in coordinating the expression of nuclear and mitochondrial genomes, linking hypusination to cancer progression.