PO-151 Variation of ribosome composition and translational reprogramming during human mammary epithelial-to-mesenchymal transition

IntroductionIt has been thought for a long time that ribosome, the machinery translating mRNAs into proteins, displays invariable intrinsic translational activity. However, it recently emerged that ribosome can act as a direct regulator of translation. Ribosome can indeed exhibit distinct composition at both protein and RNA levels that affects its three-dimensional structure on which relies its intrinsic translational activity. Our team showed that alteration of rRNA 2’-O-ribose methylation patterns display distinct translational activities, favouring the translation of a subset of mRNAs (Belin et al. Plos One 2009; Marcel et al. Cancer Cell 2013; Erales et al. PNAS 2017). At present, it remains to decipher whether translational regulation by ribosome contributes to tumorigenesis and cancer progression.In addition to transcription, it appears that translation can also play a role in Epithelial-to-Mesenchymal Transition (EMT) - the biological process that corresponds to the transdifferentiation of epithelial cells to mesenchymal ones. In cancer, EMT has been shown to promote tumorigenesis by bypassing oncogene-induced senescence and apoptosis but also to contribute in cancer progression by favouring metastasis formation and drug resistance. While transcription and epigenetic reprogramming have been largely explored in EMT, little is known about the contribution of translational reprogramming in EMT. Furthermore, the role of ribosome-induced translational reprogramming has never been explored in EMT.Material and methodsOriginal and innovative RNA- and protein-based genome-wide approaches were performed to characterise ribosome composition (RiboMETH-seq, RiboProteome) and translational reprogramming (Polysome profiles).Results and discussionsUsing OMIC approaches, we showed that epithelial and mesenchymal ribosomes exhibit different composition and we identified EMT-associated mRNAs whose translation varied between epithelial and mesenchymal cells, independently of their expression levels.ConclusionAltogether, these data highlight the concept of specialised ribosome in cancer and allow identifying EMT-derived ribosomes. We will discuss the opportunity of using such EMT-derived ribosome as innovative biomarker and therapeutic target.