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-Structure paper
タイトル | The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 7511, Year 2024 |
掲載日 | 2024年8月29日 |
![]() | Lisa Kofler / Lorenz Grundmann / Magdalena Gerhalter / Michael Prattes / Juliane Merl-Pham / Gertrude Zisser / Irina Grishkovskaya / Victor-Valentin Hodirnau / Martin Vareka / Rolf Breinbauer / Stefanie M Hauck / David Haselbach / Helmut Bergler / ![]() ![]() |
PubMed 要旨 | 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 ...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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手法 | EM (単粒子) |
解像度 | 2.6 - 3.7 Å |
構造データ | ![]() EMDB-51122: Nsa-Tap Pre-60S particle - cluster 1, combined ![]() EMDB-51126: Nsa-Tap Pre-60S particle - cluster 2, combined ![]() EMDB-51128: Nsa-Tap Pre-60S particle - cluster 3, combined ![]() EMDB-51129: Nsa-Tap Pre-60S particle - cluster 4, combined ![]() EMDB-51164: Nsa-Tap Pre-60S particle - cluster 1, untreated ![]() EMDB-51165: Nsa-Tap Pre-60S particle - cluster 2, untreated ![]() EMDB-51166: Nsa-Tap Pre-60S particle - cluster 3, untreated ![]() EMDB-51167: Nsa-Tap Pre-60S particle - cluster 4, untreated ![]() EMDB-51175: Nsa-Tap Pre-60S particle - cluster 1, treated ![]() EMDB-51176: Nsa-Tap Pre-60S particle - cluster 2, treated ![]() EMDB-51177: Nsa-Tap Pre-60S particle - cluster 3, treated ![]() EMDB-51178: Nsa-Tap Pre-60S particle - cluster 4, treated |
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