ArticleNucleic acids research2024
Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Design, Synthesis, and Antitubercular Activity of Thiolutin-Cycloserine Hybrids: Reducing Cytotoxicity.Microorganisms · 2026Article
- Hac1-independent functions of Ire1 drive morphogenesis in Candida albicans through distinct transcriptional programs.Journal of cell science · 2026Article
- Genetic dissection of transcription start site selection by RNA polymerase II in Saccharomyces cerevisiae.Genetics · 2026Article
- Thiolutin extends replicative lifespan by rewiring yeast transcription and metabolism.Scientific reports · 2026Article
- A novelFrontiers in microbiology · 2026Article
- Genetic dissection of transcription start site selection by RNA Polymerase II inbioRxiv : the preprint server for biology · 2025Article
- Intergenic accumulation of RNA polymerase II maintains the potential for swift transcriptional restart upon release from quiescence.Genome research · 2025Article
- RNase III cleavage sites spread across splice junctions enforce sequential snoRNA processing.EMBO reports · 2025Article
- Widespread epistasis shapes RNA polymerase II active site function and evolution.Nature communications · 2025Article
- Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks.Natural products and bioprospecting · 2025Review
- Reductive activation of the disulfide-containing antibiotic thiolutin is mediated by both bacillithiol and FAD-dependent disulfide reductases.Journal of bacteriology · 2025Article
- Dual Redox Targeting by Pyrroloformamide A and Silver Ions Enhances Antibacterial and Anti-Biofilm Activity Against Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2025Article
- Activation of Dithiolopyrrolone Antibiotics by Cellular Reductants.Biochemistry · 2025Article
- Biocontrol of Mycotoxigenic Fungi by Actinobacteria.Journal of fungi (Basel, Switzerland) · 2024Review
- Hibiscus acid and hydroxycitric acid dimethyl esters from Hibiscus flowers induce production of dithiolopyrrolone antibiotics by Streptomyces Strain MBN2-2.Natural products and bioprospecting · 2024Article
- 1,10-phenanthroline inhibits sumoylation and reveals that yeast SUMO modifications are highly transient.EMBO reports · 2024Article
- Dithiolopyrrolones are Prochelators that are Activated by Glutathione.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- The Association of Rpb4 with RNA Polymerase II Depends on CTD Ser5P Phosphatase Rtr1 and Influences mRNA Decay inInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Thiolutin is a natural product transcription inhibitor with an unresolved mode of action. Thiolutin and the related dithiolopyrrolone holomycin chelate Zn2+ and previous studies have concluded that RNA Polymerase II (Pol II) inhibition in vivo is indirect. Here, we present chemicogenetic and biochemical approaches to investigate thiolutin's mode of action in Saccharomyces cerevisiae. We identify mutants that alter sensitivity to thiolutin. We provide genetic evidence that thiolutin causes oxidation of thioredoxins in vivo and that thiolutin both induces oxidative stress and interacts functionally with multiple metals including Mn2+ and Cu2+, and not just Zn2+. Finally, we show direct inhibition of RNA polymerase II (Pol II) transcription initiation by thiolutin in vitro in support of classical studies that thiolutin can directly inhibit transcription in vitro. Inhibition requires both Mn2+ and appropriate reduction of thiolutin as excess DTT abrogates its effects. Pause prone, defective elongation can be observed in vitro if inhibition is bypassed. Thiolutin effects on Pol II occupancy in vivo are widespread but major effects are consistent with prior observations for Tor pathway inhibition and stress induction, suggesting that thiolutin use in vivo should be restricted to studies on its modes of action and not as an experimental tool.
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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.