Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus

被引：230

作者：

Yao, Run-Wen ^{[1
]}

Xu, Guang ^{[1
]}

Wang, Ying ^{[2
]}

Shan, Lin ^{[1
]}

Luan, Peng-Fei ^{[1
]}

Wang, Yang ^{[1
]}

Wu, Man ^{[1
]}

Yang, Liang-Zhong ^{[1
]}

Xing, Yu-Hang ^{[1
,4
,5
]}

Yang, Li ^{[2
,3
]}

Chen, Ling-Ling ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, CAS Ctr Excellence Mol Cell Sci,Shanghai Inst Bio, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, CAS Key Lab Computat Biol,CAS MPG Partner Inst Co, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[3] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China

[4] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[5] Harvard Med Sch, Boston, MA 02114 USA

来源：

MOLECULAR CELL | 2019年 / 76卷 / 05期

基金：

中国国家自然科学基金;

关键词：

POLYMERASE-I TRANSCRIPTION; QUANTITATIVE-ANALYSIS; ORGANIZER REGIONS; SSU PROCESSOME; BOX C/D; BINDING; HETEROCHROMATIN; PROTEINS; GENES; ACTIVATION;

D O I：

10.1016/j.molcel.2019.08.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：767 / +

页数：28

共 56 条

[1] Structural and thermodynamic evidence for a stabilizing role of Nop5p in S-adenosyl-L-methionine binding to fibrillarin [J].