Intricate ribosome composition and translational reprogramming in epithelial-mesenchymal transition

• 成果类型: Article
• 署名作者: Morin, Chloe; Baudin-Baillieu, Agnes; Van Long, Flora Nguyen; Isaac, Caroline; Bidou, Laure; Arbes, Hugo; Francois, Pauline; Pommier, Roxane M.; Adrait, Annie; Saku, Akari; Gran, Stephanie; Machkouri, Camelia; Vanbelle, Christophe; Morichon, Romain; Boissan, Mathieu; Catez, Frederic; Ferrari, Anthony; Morel, Anne-Pierre; Coute, Yohann; Chat, Sophie; Giudice, Emmanuel; Gillet, Reynald; Puisieux, Alain; Moyret-balle, Caroline; Diaz, Jean- Jacques; Namy, Olivier; Marcel, Virginie
• 署名单位: Centre National de la Recherche Scientifique (CNRS); UNICANCER; Centre Leon Berard; Universite Claude Bernard Lyon 1; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Claude Bernard Lyon 1; UNICANCER; Centre Leon Berard; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CEA; UNICANCER; Centre Leon Berard; Universite Claude Bernard Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Sorbonne Universite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Hopital Universitaire Charles-Foix - APHP; UNICANCER; Centre Leon Berard; Universite de Rennes; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); UNICANCER; Universite PSL; Institut Curie; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13188
• DOI: 10.1073/pnas.2408114121
• 发表日期: 2024-12-10
• 关键词: transcription factor snail; ires-mediated translation; gene-expression; laminin b1; codon readthrough; binding-protein; messenger-rnas; activation; generation; eif3

摘要

Epithelial-mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, evidence suggests that translation and ribosome composition also play key roles in establishing pathophysiological phenotypes. Using genome-wide analyses, we reported significant rearrangement of the translational landscape and machinery during EMT. Specifically, a cell line overexpressing the EMT transcription factor ZEB1 displayed alterations in translational reprogramming and fidelity. Furthermore, using riboproteomics, we unveiled an increased level of the ribosomal protein RPL36A in mesenchymal ribosomes, indicating precise tuning of ribosome composition. Remarkably, RPL36A overexpression alone was sufficient to trigger the acquisition of mesenchymal features, including a switch in the molecular pattern, cell morphology, and behavior, demonstrating its pivotal role in EMT. These findings underline the importance of translational reprogramming and fine- tuning of ribosome composition in EMT.