TY - BOOK AU - Yao,R.W. AU - Xu,G. AU - Wang,Y. AU - Shan,L. AU - Luan,P.F. AU - Wang,Y. AU - Chen,L.L. TI - Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus KW - FIBRILLARIN KW - GLYCINE- AND ARGININE-RICH KW - INTRINSICALLY DISORDERED REGION KW - RNA BINDING DOMAIN KW - RNA SORTING KW - NUCLEOLUS KW - CONDENSATES KW - RIBOSOMAL RNA KW - PHASE SEPARATION KW - SUPER-RESOLUTION MICROSCOPY N2 - 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 UR - https://drive.google.com/file/d/1kU9zWp_5Hl2xQ2ls5p-A9FZjotD9o3D2/view?usp=drivesdk ER -