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Lookup NU author(s): Lewis Chan, Chinenye Ekemezie, Charlotte Brown, Karla Helena Bueno, Dr Tom Williams, Dr Sergey MelnikovORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Authors. Drugs that target eukaryotic ribosomes are becoming increasingly important as research tools and potential therapies against cancer and pathogenic eukaryotes. However, in the absence of comparative studies, we currently do not know how many eukaryotes possess ribosomal drug-binding sites identical to those in humans and how many significantly differ from those in humans. To address this, we traced the evolutionary history of individual ribosomal drug-binding residues from the emergence of eukaryotes to the present day. We found that ribosomal drug-binding sites are divergent across eukaryotic clades, with some of the clades exhibiting more substitutions in their ribosomal drug-binding sites compared to humans than humans do compared to bacteria. Overall, our work provides a resource for understanding the evolutionary divergence of drug-binding sites in eukaryotic ribosomes, which may inform the use of ribosome inhibitors as research tools and lineage-specific drugs against eukaryotic parasites.
Author(s): Chan LI, Ekemezie CL, Brown CR, Helena-Bueno K, Williams TA, Melnikov SV
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2025
Volume: 44
Issue: 9
Print publication date: 23/09/2025
Online publication date: 11/09/2025
Acceptance date: 12/08/2025
Date deposited: 30/09/2025
ISSN (print): 2639-1856
ISSN (electronic): 2211-1247
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.celrep.2025.116244
DOI: 10.1016/j.celrep.2025.116244
Data Access Statement: Data availability: Further information in support of this work was deposited in FigShare: https://doi.org/10.6084/m9.figshare.27918987.v1. Code availability: The code used in this study to analyze rRNA polymorphism was deposited in FigShare as "Data S6": https://doi.org/10.6084/m9.figshare.27918987.v1. Additional information: Information about natural variation in ribosomal drug-binding residues for individual species is also available through this web interface: https://melnikovlab.com/check-your-species
PubMed id: 40944914
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