Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus
| Autor: | Run-Wen Yao, Yang Wang, Guang Xu, Yu-Hang Xing, Ying Wang, Ling-Ling Chen, Li Yang, Man Wu, Peng-Fei Luan, Liang-Zhong Yang, Lin Shan |
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| Rok vydání: | 2019 |
| Předmět: |
Chromosomal Proteins
Non-Histone Heterochromatin Nucleolus Active Transport Cell Nucleus Biology DNA-binding protein 03 medical and health sciences 0302 clinical medicine Transcription (biology) RNA Precursors Humans Protein Interaction Domains and Motifs RNA Processing Post-Transcriptional Molecular Biology Gene 030304 developmental biology Fibrillarin 0303 health sciences RNA Antigens Nuclear Cell Biology Ribosomal RNA Cell biology HEK293 Cells RNA Ribosomal Nucleic Acid Conformation Female Cell Nucleolus 030217 neurology & neurosurgery HeLa Cells Protein Binding |
| Zdroj: | Molecular Cell. 76:767-783.e11 |
| ISSN: | 1097-2765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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