普林斯顿大学Clifford P. Brangwynne小组近日取得一项新成果。经过不懈努力，他们报道了RNA驱动多相核仁结构的制图与工程。2025年7月2日出版的《自然》杂志发表了这项成果。

在这里，该团队开发了两种互补的方法来绘制rRNA加工的时空图和重新生成核仁。利用测序与成像并行，课题组发现rRNA加工步骤在空间上是分离的，通过核仁期向外移动需要rRNA的顺序成熟。通过在细胞中生成人工合成的核仁，该课题组发现SSU加工中的缺陷可以改变核仁阶段的顺序，导致核仁内向外并阻止rRNA的流出，而LSU前体是构建核仁最外层所必需的。这些发现证明了rRNA既是核苷的支架又是底物，rRNA作为多相结构的可编程蓝图，促进了基本分子机器的组装。

据悉，生物分子凝聚物是细胞内区隔化的关键特征。核糖体是真核生物中最重要的核凝聚体，是一种多相的液体状结构，核糖体RNA （rRNA）在其中被转录和加工，经过多个成熟步骤形成小（SSU）和大（LSU）核糖体亚基。然而，由于缺乏精确监测和干扰核仁rRNA加工动力学的工具，人们对rRNA加工如何与核仁层状组织耦合知之甚少。

附：英文原文

Title: Mapping and engineering RNA-driven architecture of the multiphase nucleolus

Author: Quinodoz, Sofia A., Jiang, Lifei, Abu-Alfa, Aya A., Comi, Troy J., Zhao, Hongbo, Yu, Qiwei, Wiesner, Lennard W., Botello, Jordy F., Donlic, Anita, Soehalim, Elizabeth, Bhat, Prashant, Zorbas, Christiane, Wacheul, Ludivine, Komrlj, Andrej, Lafontaine, Denis L. J., Klinge, Sebastian, Brangwynne, Clifford P.

Issue&Volume: 2025-07-02

Abstract: Biomolecular condensates are key features of intracellular compartmentalization1,2. As the most prominent nuclear condensate in eukaryotes, the nucleolus is a multiphase liquid-like structure in which ribosomal RNAs (rRNAs) are transcribed and processed, undergoing multiple maturation steps to form the small (SSU) and large (LSU) ribosomal subunits3,4,5. However, how rRNA processing is coupled to the layered organization of the nucleolus is poorly understood owing to a lack of tools to precisely monitor and perturb nucleolar rRNA processing dynamics. Here we developed two complementary approaches to spatiotemporally map rRNA processing and engineer de novo nucleoli. Using sequencing in parallel with imaging, we found that rRNA processing steps are spatially segregated, with sequential maturation of rRNA required for its outward movement through nucleolar phases. By generating synthetic nucleoli in cells using an engineered rDNA plasmid system, we show that defects in SSU processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux, while LSU precursors are necessary to build the outermost layer of the nucleolus. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine.

DOI: 10.1038/s41586-025-09207-4

Source: https://www.nature.com/articles/s41586-025-09207-4