Nascent Pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus
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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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The transcriptionally inert rDNA genes associated with HP1 have been demonstrated inside active human NORs by super-resolution microscopy.
“Moreover, the transcriptionally inert rDNA genes associated with HP1 have been recently demonstrated inside active human NORs by super-resolution microscopy (105).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [105]
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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
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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