期刊
MOLECULAR CELL
卷 76, 期 5, 页码 767-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.08.014
关键词
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资金
- 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 [55008728]
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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