ArticleNature cell biology2024
Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- METTL1-mediated m7G modification of valine tRNAs drives metabolic adaptation in pancreatic ductal adenocarcinoma cells.The Journal of clinical investigation · 2026Article
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- In Vivo Efficacy and Biochemical Target Engagement of a Chromene-Based Inhibitor of Trypanosoma cruzi Lysyl-tRNA Synthetase.Journal of medicinal chemistry · 2026Article
- Nuclear localization of the glutaminyl-tRNA synthetase QARS reveals its role in DNA damage response in ovarian cancer.Nature communications · 2026Article
- Neuroprotective role of Curcuma amada evidenced from pesticide-induced stressed Drosophila melanogaster: insights from RNAseq and gut microbiome analyses.Molecular genetics and genomics : MGG · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- DARS expression in JAK2V617F-positive myeloproliferative neoplasms: immunohistochemical analysis and clinical associations.Annals of hematology · 2026Article
- Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint.Journal of translational medicine · 2026Article
- Transfer RNA expression, modification, and derived small RNAs in cancer biology and clinical potential.Frontiers in immunology · 2026Review
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- Non-coding RNAs in programmed cell death regulation in melanoma: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Interpreting ribosome dynamics during mRNA translation.The Journal of biological chemistry · 2025Review
- Article
- Integrating Machine Learning Algorithms to Construct a Triaptosis-Related Prognostic Model in Melanoma.Cancer management and research · 2025Article
- Metabolic reprogramming-driven stratification and therapeutic targeting in lung adenocarcinoma: implications for prognosis and personalized treatment.Frontiers in oncology · 2025Article
- Decoding the role of tRNA modifications in cancer progression.Current opinion in genetics & development · 2024Review
- Translational control by VARS in melanoma.Nature cell biology · 2024Article
- Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
Transfer RNA dynamics contribute to cancer development through regulation of codon-specific messenger RNA translation. Specific aminoacyl-tRNA synthetases can either promote or suppress tumourigenesis. Here we show that valine aminoacyl-tRNA synthetase (VARS) is a key player in the codon-biased translation reprogramming induced by resistance to targeted (MAPK) therapy in melanoma. The proteome rewiring in patient-derived MAPK therapy-resistant melanoma is biased towards the usage of valine and coincides with the upregulation of valine cognate tRNAs and of VARS expression and activity. Strikingly, VARS knockdown re-sensitizes MAPK-therapy-resistant patient-derived melanoma in vitro and in vivo. Mechanistically, VARS regulates the messenger RNA translation of valine-enriched transcripts, among which hydroxyacyl-CoA dehydrogenase mRNA encodes for a key enzyme in fatty acid oxidation. Resistant melanoma cultures rely on fatty acid oxidation and hydroxyacyl-CoA dehydrogenase for their survival upon MAPK treatment. Together, our data demonstrate that VARS may represent an attractive therapeutic target for the treatment of therapy-resistant melanoma.
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Registered trials
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.