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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cryo-em; Rna Exosome; Protein; Versatile; Pathway; Stress; Cells
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 7511 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-505700-001
A-630700-001
Förderungen 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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