前駆rRNA処理と核小体構造の時空間的協調を解明(Researchers Reveal Spatiotemporal Coordination Between Pre-rRNA Processing and Nucleolar Architecture)

2025-07-29 中国科学院(CAS)

<関連情報>

• https://english.cas.cn/newsroom/research_news/life/202507/t20250728_1048553.shtml
• https://www.nature.com/articles/s41586-025-09412-1

前体リボソームRNA(pre-rRNA)の空間的分布と核小体の機能的組織化 Pre-rRNA spatial distribution and functional organization of the nucleolus

Yu-Hang Pan,Lin Shan,Yu-Yao Zhang,Zheng-Hu Yang,Yuan Zhang,Shi-Meng Cao,Xiao-Qi Liu,Jun Zhang,Li Yang & Ling-Ling Chen
Nature  Published:23 July 2025
DOI:https://doi.org/10.1038/s41586-025-09412-1

Abstract

The multi-layered nucleolus serves as the primary site of ribosome biogenesis^1,2, 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 understood^6,7. 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 compartments^8,9 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.