2026年10月29日，德国欧洲分子生物学实验室Xiaohan Zhao等科学家在《科学》（Science）发表研究，利用冷冻关联光镜与电子断层扫描技术，在HeLa细胞核仁内可视化人类前核糖体的组装过程。

在真核生物中，核糖体生物发生在核仁内启动，核仁是细胞核中标志性的多层区室。前核糖体结构已在离体条件下得到表征，但其在人类核仁内的组装途径尚未被描述。在此，研究人员利用冷冻关联光镜与电子断层扫描技术，可视化HeLa细胞核仁内的分子景观，并获得了两种核糖体亚基前体——小亚基加工体（SSU processome）和前60S——的细胞内结构快照。这些快照重现了此前在离体条件下解析的主要状态，并揭示了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。研究人员进一步表明，RNA聚合酶I抑制后前核糖体组装景观如何发生改变。该研究将分子结构与细胞背景相结合，阐明了人类核糖体的时空组装途径。

附：英文原文

Title: In-cell structures visualize human pre-ribosome assembly in the nucleolus

Author: Xiaohan Zhao, Yuki Hayashi, Herman K. H. Fung, Sara Cuylen-Haering, Julia Mahamid, Christoph W. Müller

Issue&Volume: 2026-10-29

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 small subunit 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.

DOI: 10.1126/science.aej0483

Source:https://www.science.org/doi/10.1126/science.aej0483