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Kofler, L.* ; Grundmann, L.* ; Gerhalter, M.* ; Prattes, M.* ; Merl-Pham, J. ; Zisser, G.* ; Grishkovskaya, I.* ; Hodirnau, V.V.* ; Vareka, M.* ; Breinbauer, R.* ; Hauck, S.M. ; Haselbach, D.* ; Bergler, H.*

The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation.

Nat. Commun. 15:7511 (2024)
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The formation of new ribosomes is tightly coordinated with cell growth and proliferation. In eukaryotes, the correct assembly of all ribosomal proteins and RNAs follows an intricate scheme of maturation and rearrangement steps across three cellular compartments: the nucleolus, nucleoplasm, and cytoplasm. We demonstrate that usnic acid, a lichen secondary metabolite, inhibits the maturation of the large ribosomal subunit in yeast. We combine biochemical characterization of pre-ribosomal particles with a quantitative single-particle cryo-EM approach to monitor changes in nucleolar particle populations upon drug treatment. Usnic acid rapidly blocks the transition from nucleolar state B to C of Nsa1-associated pre-ribosomes, depleting key maturation factors such as Dbp10 and hindering pre-rRNA processing. This primary nucleolar block rapidly rebounds on earlier stages of the pathway which highlights the regulatory linkages between different steps. In summary, we provide an in-depth characterization of the effect of usnic acid on ribosome biogenesis, which may have implications for its reported anti-cancer activities.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cryo-em; Rna Exosome; Protein; Versatile; Pathway; Stress; Cells
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 7511 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505700-001
A-630700-001
Grants Austrian Research Promotion Agency
Boehringer Ingelheim
Austrian Science Foundation
Scientific Service Units of IST Austria
DOI 10.1038/s41467-024-51754-3
WOS ID 001457895200001
Scopus ID 85202844190
PubMed ID 39209816
Erfassungsdatum 2024-10-09
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