中国科学院大学陈玲玲小组在研究中取得进展。他们提出了核仁Pre-rRNA的空间分布与功能组织。这一研究成果发表在2025年7月23日出版的国际学术期刊《自然》上。

多层核糖体是核糖体生物发生的主要位点，在这里发生小亚基（SSU）和大亚基（LSU）前体的连续成熟。

然而，pre-rRNA加工和核仁亚结构之间的空间功能关系以及这种关系如何适应不断变化的细胞生理需求仍然不完全清楚。他们的时空分析揭示了人类核仁中一个区室特异性核糖体亚基加工，SSU过程体维持在纤维中心/致密纤维组分/周围致密纤维组分（FC/DFC/PDFC）区域，而LSU前体RNA大部分转移到PDFC/颗粒组分（GC）区域。增殖缓慢的细胞表现出意想不到的5'端外部转录空间（5' ETS）为中心的SSU加工损伤，伴随着FC/DFC结构重塑和SSU输出迟缓。直接5' ETS加工扰动至少部分再现了这些FC/DFC变化，支持了SSU加工和核核结构之间的功能相互依赖关系。

值得注意的是，与羊膜动物多层核仁相比，非羊膜动物融合FC/DFC区室的双分核仁表现出独特的5' ETS分布模式和更慢的前体rRNA流动速率。在两部核仁中引入FC/DFC接口可提高加工效率，表明嵌套FC/DFC的进化出现可能优化了pre-rRNA加工。总的来说，通过描绘前体rRNA的时空分布规律，研究揭示了以5' ETS为核心的SSU加工对维持核仁亚结构的关键作用，并提示多层结构可能为羊膜动物带来的进化优势。

附：英文原文

Title: Pre-rRNA spatial distribution and functional organization of the nucleolus

Author: Pan, Yu-Hang, Shan, Lin, Zhang, Yu-Yao, Yang, Zheng-Hu, Zhang, Yuan, Cao, Shi-Meng, Liu, Xiao-Qi, Zhang, Jun, Yang, Li, Chen, Ling-Ling

Issue&Volume: 2025-07-23

Abstract: The multi-layered nucleolus serves as the primary site of ribosome biogenesis1,2, where successive maturation of small (SSU)3,4 and large (LSU)5 ribosomal subunit precursors occur. However, the spatio-functional relationship between pre-rRNA processing and nucleolar substructures and how this adapts to changing cellular physiological demands have remained incompletely understood6,7. Here, our spatiotemporal analyses revealed a compartment-specific ribosomal subunit processing in human nucleoli, with SSU processomes maintained in fibrillar center/dense fibrillar component/periphery dense fibrillar component (FC/DFC/PDFC) domains while LSU pre-rRNAs largely transited to PDFC/granular component (GC) regions. Slow proliferating cells exhibited unexpected 5' external transcribed space (5' ETS)-centered SSU processing impairment, accompanied by FC/DFC structural remodeling and retarded SSU outflux. Direct 5' ETS processing perturbation at least partially recapitulated these FC/DFC alterations, supporting the functional interdependence between SSU processing and nucleolar architecture. Notably, anamniote bipartite nucleoli with merged FC/DFC compartments8,9 exhibited distinct 5' ETS distribution and slower pre-rRNA flux compared to multi-layered nucleoli in amniotes. Introducing a FC/DFC interface to bipartite nucleoli enhanced processing efficiency, indicating that evolutionary emergence of nested FC/DFC may have optimized pre-rRNA processing. Collectively, depicting the spatiotemporal distribution of pre-rRNAs revealed an essential role of 5' ETS-centered SSU processing in maintaining nucleolar substructures and suggested a possible evolutionary advantage of the multi-layered structure in amniotes.

DOI: 10.1038/s41586-025-09412-1

Source: https://www.nature.com/articles/s41586-025-09412-1