Cited by 327Nuclear Structure and FunctionRNA Research and SplicingGenomics and Chromatin Dynamics

Nascent Pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus

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Yao, Run-Wen, Xu, Guang, Wang, Ying, Shan, Lin, Luan, Peng-Fei, Wang, Yang, Wu, Man, Yang, Liang-Zhong +3 more·2019·Molecular Cell

Abstract

Fibrillar centers (FCs) and dense fibrillar components (DFCs) are essential morphologically distinct sub-regions of mammalian cell nucleoli for rDNA transcription and pre-rRNA processing. Here, we report that a human nucleolus consists of several dozen FC/DFC units, each containing 2-3 transcriptionally active rDNAs at the FC/DFC border. Pre-rRNA processing factors, such as fibrillarin (FBL), form 18-24 clusters that further assemble into the DFC surrounding the FC. Mechanistically, the 5' end of nascent 47S pre-rRNA binds co-transcriptionally to the RNA-binding domain of FBL. FBL diffuses to the DFC, where local self-association via its glycine- and arginine-rich (GAR) domain forms phase-separated clusters to immobilize FBL-interacting pre-rRNA, thus promoting directional traffic of nascent pre-rRNA while facilitating pre-rRNA processing and DFC formation. These results unveil FC/DFC ultrastructures in nucleoli and suggest a conceptual framework for considering nascent RNA sorting using multivalent interactions of their binding proteins.

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Crossref · 10.1016/j.molcel.2019.08.014

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Authors
Yao, R.-W., Xu, G., Wang, Y., Shan, L., Luan, P.-F., Wang, Y., Wu, M., Yang, L.-Z., Xing, Y.-H., Yang, L., & Chen, L.-L.
Affiliations
  • Center for Excellence in Molecular Cell Science (CN)
  • Shanghai Institute of Nutrition and Health (CN)
  • ShanghaiTech University (CN)
Corresponding author
Chen, Ling-Ling
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-12
Volume
76
Issue
5
Pages
767-783.e11
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2973637866
Cited by
327
References
56
Citations by year
2026: 36 · 2025: 50 · 2024: 74 · 2023: 51 · 2022: 34 · 2021: 50 · 2020: 30 · 2019: 2
FWCI
9.59
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Science and Technology of China (2016YFA0100701)
  • Chinese Academy of Sciences (XDB19020104)
  • National Natural Science Foundation of China (31861143025, 31830108, 31821004, 31725009, 31730111)
  • HHMI International Research Scholar Program (55008728)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
nucleolus, fibrillar centers, dense fibrillar component, pre-rRNA processing, phase separation, fibrillarin, rDNA transcription, RNA-binding domain, multivalent interactions
MeSH terms
Cell Nucleolus, Chromosomal Proteins, Non-Histone, Female, HeLa Cells, Humans, Nucleic Acid Conformation, Protein Binding, RNA Precursors, RNA Processing, Post-Transcriptional, RNA, Ribosomal, Active Transport, Cell Nucleus, Antigens, Nuclear, Protein Interaction Domains and Motifs, HEK293 Cells

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