ArticlePLoS genetics2014
tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 184 citations in OpenAlex.
- RNA modifications in cancer and their detection: a review.Japanese journal of clinical oncology · 2026Review
- Structure-Based Simulations for Folding of a tRNA Isodecoder.Molecules (Basel, Switzerland) · 2026Article
- Long Noncoding RNA Isoform Specificity and Chemical Modification on tRNA-Derived Fragments Leading to Divergent Functions.The American journal of pathology · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- NSUN2 promoted tumor growth and metastatic via mCell death & disease · 2026Article
- m7G RNA methylation in cancer: Effect, mechanism and clinical application.Clinical and translational medicine · 2025Review
- NSUN2 promotes leukemogenesis by ferritin heavy chain 1-mediated anti-ferroptosis and enhancing global protein synthesis in an mClinical epigenetics · 2025Article
- m7G-related gene signatures determine prognosis in triple-negative breast cancer.Scientific reports · 2025Article
- tsRNA modifications: An emerging layer of biological regulation in disease.Journal of advanced research · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Application and clinical translational value of a predictive model based on NOncology letters · 2025Article
- 5-Methylcytosine RNA modification and its roles in cancer and cancer chemotherapy resistance.Journal of translational medicine · 2025Review
- NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment.Nucleic acids research · 2025Article
- tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus.Nucleic acids research · 2025Article
- Post-Translational Modifications of RNA-Modifying Proteins in Cellular Dynamics and Disease Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.Cell communication and signaling : CCS · 2024Review
- METTL protein family: focusing on the occurrence, progression and treatment of cancer.Biomarker research · 2024Review
- Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets.Cell proliferation · 2024Review
- Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy.Journal of experimental & clinical cancer research : CR · 2024Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay (RTD). The tRNA modifying enzymes, NSUN2 and METTL1, are mammalian orthologs of yeast Trm4 and Trm8, which are required for protecting tRNA against RTD. A simultaneous overexpression of NSUN2 and METTL1 is widely observed among human cancers suggesting that targeting of both proteins provides a novel powerful strategy for cancer chemotherapy. Here, we show that combined knockdown of NSUN2 and METTL1 in HeLa cells drastically potentiate sensitivity of cells to 5-fluorouracil (5-FU) whereas heat stress of cells revealed no effects. Since NSUN2 and METTL1 are phosphorylated by Aurora-B and Akt, respectively, and their tRNA modifying activities are suppressed by phosphorylation, overexpression of constitutively dephosphorylated forms of both methyltransferases is able to suppress 5-FU sensitivity. Thus, NSUN2 and METTL1 are implicated in 5-FU sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-FU chemotherapy of cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.