细胞内结构可视化人类核仁中前核糖体组装
In-cell structures visualize human pre-ribosome assembly in the nucleolus
在真核生物中，核糖体生物合成始于细胞核内的核仁。此前前核糖体结构多在离体条件下解析，但其在人类核仁内的组装路径尚未被描述。研究使用冷冻关联光与电子断层扫描技术，可视化HeLa细胞核仁内的分子景观，获得了核糖体大小亚基前体（SSU processome和pre-60S）的细胞内结构快照。这些结构重现了此前离体解析的主要状态，并揭示额外的关键相互作用伙伴，包括RNA外切体、rixosome和核输出受体CRM1-RanGTP。研究还展示了抑制RNA聚合酶I后前核糖体组装景观的变化。该研究将分子结构与细胞环境结合，阐明人类核糖体的时空组装路径。
为什么推荐给您：首次在细胞内原位解析人类核仁前核糖体组装，属重要新方法揭示的基础机制发现。
不需要生物学背景，多打比方
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摘要Abstract
In eukaryotes, ribosome biogenesis initiates within the nucleolus, a hallmark multilayered compartment of the nucleus. Structures of pre-ribosomes have been characterized ex situ, but their assembly pathways within human nucleoli have not been described. Here, we used cryogenic correlative light and electron tomography to visualize molecular landscapes within HeLa cell nucleoli and obtained in-cell structural snapshots of both ribosomal subunit precursors, the SSU processome and the pre-60S. These recapitulate major states resolved previously ex situ and reveal additional critical interaction partners, including the RNA exosome, rixosome, and nuclear export receptor CRM1-RanGTP. We further show how pre-ribosome assembly landscapes are altered upon RNA polymerase I inhibition. Our study combines molecular structures with cellular context to elucidate the spatiotemporal assembly pathway of the human ribosome.