Molecular cell, 2019-12, Vol.76 (5), p.767-783.e11
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus
- Ist Teil von
- Molecular cell, 2019-12, Vol.76 (5), p.767-783.e11
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2019
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- 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. [Display omitted] •Visualizing the ultrastructure of FC/DFC and rDNA arrangements in human nucleoli•Processing factors, such as FBL, form protein clusters and then assemble into a DFC•Self-association of GAR in FBL ensures sorting and processing of nascent 47S pre-rRNA•Nascent pre-rRNA sorting via a phase-separation mechanism promotes DFC assembly Yao et al. unveil the FC/DFC ultrastructure and rDNA arrangements in human nucleoli and show that a phase-separation mechanism promotes nascent pre-rRNA sorting and processing and the assembly of the DFC sub-nucleolar region.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2019.08.014Titel-ID: cdi_proquest_miscellaneous_2295484984
- Format
- –
- Schlagworte
- Active Transport, Cell Nucleus, Antigens, Nuclear - genetics, Antigens, Nuclear - metabolism, Cell Nucleolus - genetics, Cell Nucleolus - metabolism, Cell Nucleolus - ultrastructure, Chromosomal Proteins, Non-Histone - genetics, Chromosomal Proteins, Non-Histone - metabolism, condensates, Female, Fibrillarin, glycine- and arginine-rich, HEK293 Cells, HeLa Cells, Humans, intrinsically disordered region, Nucleic Acid Conformation, nucleolus, phase separation, Protein Binding, Protein Interaction Domains and Motifs, ribosomal RNA, RNA binding domain, RNA Precursors - genetics, RNA Precursors - metabolism, RNA Precursors - ultrastructure, RNA Processing, Post-Transcriptional, RNA sorting, RNA, Ribosomal - genetics, RNA, Ribosomal - metabolism, RNA, Ribosomal - ultrastructure, super-resolution microscopy