{"date_created":"2024-09-08T22:01:10Z","has_accepted_license":"1","day":"29","quality_controlled":"1","language":[{"iso":"eng"}],"article_processing_charge":"Yes","doi":"10.1038/s41467-024-51754-3","volume":15,"intvolume":"        15","acknowledged_ssus":[{"_id":"EM-Fac"}],"ddc":["570"],"month":"08","scopus_import":"1","oa_version":"Published Version","publication":"Nature Communications","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2024-09-09T08:56:12Z","file":[{"success":1,"creator":"dernst","file_id":"17946","file_name":"2024_NatureComm_Kofler.pdf","date_updated":"2024-09-09T08:56:12Z","access_level":"open_access","content_type":"application/pdf","file_size":3735024,"date_created":"2024-09-09T08:56:12Z","relation":"main_file","checksum":"7c044538a47182c826d1b526c52958a2"}],"type":"journal_article","article_number":"7511","status":"public","title":"The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation","acknowledgement":"We thank Michael A. McAlear, Micheline Fromont-Racin, Philipp Milkereit, Arlen W. Johnson, Sabine Rospert, Ed Hurt, C. Yam, Günter Daum, Wolfgang Zachariae, Katrin Karbstein, Juan P. G. Ballesta, Mercedes Dosil, Miguel Remacha und Jesus de la Cruz for sharing strains or providing antibodies. We thank the members of the Bergler lab and the Haselbach lab for their helpful discussion. We thank Ellen Zhong for helpful discussions about the quantitative cryoDRGN analysis. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Electron Microscopy Facility. This research was funded in whole, or in part, by the Austrian Science Foundation grants [https://doi.org/10.55776/P32977], [https://doi.org/10.55776/P29451] and [https://doi.org/10.55776/P32536] (to H.B.). Research at the IMP is generously supported by Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","date_updated":"2024-09-09T08:56:59Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["2041-1723"]},"abstract":[{"lang":"eng","text":"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."}],"citation":{"chicago":"Kofler, Lisa, Lorenz Grundmann, Magdalena Gerhalter, Michael Prattes, Juliane Merl-Pham, Gertrude Zisser, Irina Grishkovskaya, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-51754-3\">https://doi.org/10.1038/s41467-024-51754-3</a>.","short":"L. Kofler, L. Grundmann, M. Gerhalter, M. Prattes, J. Merl-Pham, G. Zisser, I. Grishkovskaya, V.-V. Hodirnau, M. Vareka, R. Breinbauer, S.M. Hauck, D. Haselbach, H. Bergler, Nature Communications 15 (2024).","ieee":"L. Kofler <i>et al.</i>, “The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","apa":"Kofler, L., Grundmann, L., Gerhalter, M., Prattes, M., Merl-Pham, J., Zisser, G., … Bergler, H. (2024). The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-51754-3\">https://doi.org/10.1038/s41467-024-51754-3</a>","ista":"Kofler L, Grundmann L, Gerhalter M, Prattes M, Merl-Pham J, Zisser G, Grishkovskaya I, Hodirnau V-V, Vareka M, Breinbauer R, Hauck SM, Haselbach D, Bergler H. 2024. The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. Nature Communications. 15, 7511.","mla":"Kofler, Lisa, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>, vol. 15, 7511, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-51754-3\">10.1038/s41467-024-51754-3</a>.","ama":"Kofler L, Grundmann L, Gerhalter M, et al. The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-51754-3\">10.1038/s41467-024-51754-3</a>"},"department":[{"_id":"EM-Fac"}],"author":[{"full_name":"Kofler, Lisa","last_name":"Kofler","first_name":"Lisa"},{"full_name":"Grundmann, Lorenz","first_name":"Lorenz","last_name":"Grundmann"},{"first_name":"Magdalena","last_name":"Gerhalter","full_name":"Gerhalter, Magdalena"},{"full_name":"Prattes, Michael","first_name":"Michael","last_name":"Prattes"},{"full_name":"Merl-Pham, Juliane","last_name":"Merl-Pham","first_name":"Juliane"},{"full_name":"Zisser, Gertrude","last_name":"Zisser","first_name":"Gertrude"},{"last_name":"Grishkovskaya","first_name":"Irina","full_name":"Grishkovskaya, Irina"},{"last_name":"Hodirnau","first_name":"Victor-Valentin","full_name":"Hodirnau, Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3904-947X"},{"full_name":"Vareka, Martin","last_name":"Vareka","first_name":"Martin"},{"full_name":"Breinbauer, Rolf","last_name":"Breinbauer","first_name":"Rolf"},{"full_name":"Hauck, Stefanie M.","first_name":"Stefanie M.","last_name":"Hauck"},{"full_name":"Haselbach, David","last_name":"Haselbach","first_name":"David"},{"full_name":"Bergler, Helmut","last_name":"Bergler","first_name":"Helmut"}],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"Springer Nature","article_type":"original","publication_status":"published","_id":"17885","date_published":"2024-08-29T00:00:00Z","year":"2024","oa":1}