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Poster De Conférence Année : 2023

Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance

Alexandre David
Julie Pannequin

Résumé

Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used che- motherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incor- porated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5′ -untranslated region. The translational selectivity was determined by bioinformatic analysis of deep sequencing data that combine RNA-seq of both the cytosomal and polysomal fractions of mRNAs. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Alto- gether, our results demonstrate that man-made fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes. This work has been published in 2022 in Nature Communications [1].
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Dates et versions

hal-04286476 , version 1 (15-11-2023)

Identifiants

  • HAL Id : hal-04286476 , version 1

Citer

Gabriel Therizols, Zeina Bash-Imam, Baptiste Panthu, Christelle Machon, Anne Vincent, et al.. Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance. JOBIM 2023 - Journées Ouvertes en Biologie, Informatique et Mathématiques, Jun 2023, Nice, France. , pp.100. ⟨hal-04286476⟩
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