ArticleNucleic acids research2024
Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The Role of ZNF598 in Translational Quality Control: Mechanisms and Emerging Biological Functions.Biology · 2026Review
- Review
- 5-Azacytidine incorporation into mRNAs disrupts translation and induces ribosome collisions.bioRxiv : the preprint server for biology · 2026Article
- AquIRE reveals the mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAs.Nucleic acids research · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- The mTORC2 component SIN1 post-transcriptionally regulates TYMS levels and modulates P53 activity in response to 5-FU chemotherapy.Cell communication and signaling : CCS · 2026Article
- Causes and consequences of RNA:protein cross-links - lessons from chemotherapy.Emerging topics in life sciences · 2025Review
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
- NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment.Nucleic acids research · 2025Article
- Article
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Authors and funding
23 authors.
Funding
Abstract
Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant of 5FU's anticancer activity is its misincorporation into RNAs, the mechanisms by which cancer cells overcome the RNA-dependent 5FU toxicity remain ill-defined. Here, we report a role for RQC in mitigating the cytotoxic effects of 5FU. We show that 5FU treatment results in rapid induction of the mTOR signalling pathway, enhanced rate of mRNA translation initiation, and increased ribosome collisions. Consistently, a defective RQC exacerbates the 5FU-induced cell death, which is mitigated by blocking mTOR pathway or mRNA translation initiation. Furthermore, 5FU treatment enhances the expression of the key RQC factors ZNF598 and GIGYF2 via an mTOR-dependent post-translational mechanism. This adaptation likely mitigates the cytotoxic consequences of increased ribosome collisions upon 5FU treatment.
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