小柯机器人

中国科学院分子细胞卓越中心陈玲玲团队近期取得重要研究进展，他们研究发现核仁URB1确保3' ETS rRNA去除以防止外泌体监测。相关研究成果2023年3月8日在线发表于《自然》杂志上。

据介绍，核仁是细胞核中最突出的无膜凝聚物。它包含数百种蛋白质，在核糖体RNA（rRNA）的快速转录和在包括原纤维中心和致密原纤维组分以及颗粒组分中的核糖体组装的单元内的有效处理中具有不同的作用。由于成像研究中分辨率不足，大多数核仁蛋白的精确定位以及它们的特异定位是否有助于rRNA前体处理的径向通量仍然未知。因此，这些核仁蛋白如何在功能上与逐步的rRNA前处理相协调需要进一步的研究。

研究人员使用高分辨率活细胞显微镜筛选了200种候选核仁蛋白，并鉴定出12种向致密原纤维成分（PDFC）外围富集的蛋白。在这些蛋白质中，不健康的核糖体生物发生1（URB1）是一种静态的核仁蛋白质，它确保3′端rRNA前体的锚定和折叠，以识别U8小核仁RNA，并随后去除致密原纤维组分PDFC边界处的3′外转录间隔物（ETS）。URB1耗竭导致PDFC中断、rRNA前体运动不受控制、rRNA前体构象改变和3′ETS的保留。这些异常的3′ETS连接的rRNA前体中间体激活了外泌体依赖的核仁监测，导致28S rRNA产生减少、斑马鱼头部畸形和小鼠胚胎发育延迟。

总之，这项研究提供了对功能性亚核仁组织的深入了解，并确定了rRNA成熟的生理学关键步骤，该步骤需要在相分离核仁中的静态蛋白URB1。

附：英文原文

Title: Nucleolar URB1 ensures 3′ ETS rRNA removal to prevent exosome surveillance

Author: Shan, Lin, Xu, Guang, Yao, Run-Wen, Luan, Peng-Fei, Huang, Youkui, Zhang, Pei-Hong, Pan, Yu-Hang, Zhang, Lin, Gao, Xiang, Li, Ying, Cao, Shi-Meng, Gao, Shuai-Xin, Yang, Zheng-Hu, Li, Siqi, Yang, Liang-Zhong, Wang, Ying, Wong, Catharine C. L., Yu, Li, Li, Jinsong, Yang, Li, Chen, Ling-Ling

Issue&Volume: 2023-03-08

Abstract: The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component1. The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies2,3,4,5. Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3′ end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3′ external transcribed spacer (ETS) at the dense fibrillar component–PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3′ ETS. These aberrant 3′ ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus.

DOI: 10.1038/s41586-023-05767-5

Source: https://www.nature.com/articles/s41586-023-05767-5

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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