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Nascent Pre-rRNA Sorting via Phase Separation Drives the Assembly of Dense Fibrillar Components in the Human Nucleolus.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-09-17 , DOI: 10.1016/j.molcel.2019.08.014
Run-Wen Yao 1 , Guang Xu 1 , Ying Wang 2 , Lin Shan 1 , Peng-Fei Luan 1 , Yang Wang 1 , Man Wu 1 , Liang-Zhong Yang 1 , Yu-Hang Xing 1 , Li Yang 3 , Ling-Ling Chen 4
Affiliation  

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.

中文翻译:

初相rRNA通过相分离进行分选可驱动人核中密集的原纤维成分的组装。

原纤维中心(FCs)和致密原纤维成分(DFCs)是哺乳动物细胞核仁在rDNA转录和rRNA加工前必不可少的形态学上不同的子区域。在这里,我们报道一个人的核仁由几十个FC / DFC单元组成,每个单元在FC / DFC边界包含2-3个转录活性rDNA。rRNA之前的加工因子(例如原纤维蛋白(FBL))形成18-24个簇,这些簇进一步组装到FC周围的DFC中。从机制上讲,新生的47S pre-rRNA的5'末端与FBL的RNA结合结构域共转录结合。FBL扩散到DFC,在此处通过其富含甘氨酸和精氨酸的(GAR)域进行局部自缔合,形成相分离的簇,以固定与FBL相互作用的pre-rRNA,因此,在促进前rRNA加工和DFC形成的同时,促进新生pre-rRNA的定向运输。这些结果揭示了核仁中的FC / DFC超微结构,并提出了一个概念框架,用于考虑利用其结合蛋白的多价相互作用进行新生RNA分选。
更新日期:2019-09-18
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