ArticleNucleic acids research2023
Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Emerging Roles of tRNA Modifications in Translational Adaptation of Human Fungal Pathogens.Microorganisms · 2026Review
- Suboptimal codon pairs trigger ribosome collisions and cellular quality control responses in tRNA modification mutants.Nucleic acids research · 2025Article
- RNA modification is the mark and strategy for host-microbe interactions.Cellular and molecular life sciences : CMLS · 2025Review
- tRNA binding to Kti12 is crucial for wobble uridine modification by Elongator.Nucleic acids research · 2025Article
- tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus.Nucleic acids research · 2025Article
- tRNA thiolation optimizes appressorium-mediated infection by enhancing codon-specific translation in Magnaporthe oryzae.Nucleic acids research · 2025Article
- Past, Present, and Future of RNA Modifications in Infectious Disease Research.ACS infectious diseases · 2024Article
- Molecular basis for thiocarboxylation and release of Urm1 by its E1-activating enzyme Uba4.Nucleic acids research · 2024Article
- A highly conserved tRNA modification contributes toMicrobiology spectrum · 2024Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate. Ncs2 is essential for 2-thiolation of tRNA and the NCS2* mutation leads to increased thiolation at body temperature. NCS2* yeast exhibits enhanced fitness when grown at elevated temperatures or when exposed to oxidative stress, inhibition of nutrient signalling, and cell-wall stress. Importantly, Ncs2* alters the interaction and stability of the thiolase complex likely mediated by nucleotide binding. The absence of 2-thiolation abrogates the in vivo virulence of pathogenic baker's yeast in infected mice. Finally, hypomodification triggers changes in colony morphology and hyphae formation in the common commensal pathogen Candida albicans resulting in decreased virulence in a human cell culture model. These findings demonstrate that 2-thiolation of tRNA acts as a key mediator of fungal virulence and reveal new mechanistic insights into the function of the highly conserved tRNA-thiolase complex.
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