ArticleNucleic acids research2025
NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Ribosome Heterogeneity in Plants: The Causes of This Phenomenon and Its Implications on Gene Expression.Plants (Basel, Switzerland) · 2026Review
- Evaluation of Dorado v5.2.0 de novo basecalling models for the detection of tRNA modifications using RNA004 chemistry.BMC genomics · 2026Article
- AquIRE reveals the mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAs.Nucleic acids research · 2026Article
- The Rare RNA Methylations m²G, Cm, m⁵U and ms²i⁶A: Roles in Disease Pathogenesis and Emerging Therapeutic Implications.International journal of medical sciences · 2026Review
- Causes and consequences of RNA:protein cross-links - lessons from chemotherapy.Emerging topics in life sciences · 2025Review
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Authors and funding
3 authors.
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Abstract
Recent studies have investigated RNA modifications in response to stressors like chemical agents, including the anticancer drug 5-fluorouracil (5-FU). Traditionally, 5-FU's mechanism of action was believed to involve inhibition of thymidylate synthase, leading to thymidine depletion and cancer cell death. However, recent findings suggest that ribosome collisions and defects in ribosomal RNA (rRNA) processing drive 5-FU toxicity, potentially through RNA writer inhibition. To explore the effects of 5-FU on rRNA and transfer RNA (tRNA) modifications, we exposed HEK293T cells to 5-FU and quantified key RNA modifications. We found 55% and 40% reduction in 5-methyluridine and pseudouridine (Ψ), respectively, in tRNAs, but only minor changes in rRNA. Using nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS), we identified that pre-existing tRNA and rRNA retained their modification profiles, while newly synthesized RNAs lost various modifications. In addition, new tRNAs exhibited modification reprogramming, particularly important for cell survival after 5-FU removal. In rRNA, we observed reduced levels of mature rRNA, with hypomodification in newly transcribed mature rRNA, particularly in Ψ and ribose methylations. In summary, we observe RNA hypomodification in both tRNA and rRNA due to 5-FU, which might be the molecular basis of 5-FU's mechanism of action.
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