The roles of FUS-RNA binding domain and low complexity domain in RNA-dependent phase separation

被引：6

作者：

Ganser, Laura R. ^{[1
]}

Niaki, Amirhossein Ghanbari ^{[1
]}

Yuan, Xincheng ^{[1
,2
,3
]}

Huang, Ethan ^{[1
]}

Deng, Dahlia ^{[2
,3
]}

Djaja, Nathalie A. ^{[1
,2
,3
]}

Ge, Yingda ^{[1
]}

Craig, Alanna ^{[1
]}

Langlois, Olivia ^{[1
]}

Myong, Sua ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Program Cell Mol Dev Biol & Biophys, 3400 N Charles St, Baltimore, MD 21218 USA

[3] Johns Hopkins Univ, Dept Biol, 3400 N Charles St, Baltimore, MD 21218 USA

来源：

STRUCTURE | 2024年 / 32卷 / 02期

关键词：

GRANULES; STRESS; TDP-43;

D O I：

10.1016/j.str.2023.11.006

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：

Fused in sarcoma (FUS) is an archetypal phase separating protein asymmetrically divided into a low complexity domain (LCD) and an RNA binding domain (RBD). Here, we explore how the two domains contribute to RNA -dependent phase separation, RNA recognition, and multivalent complex formation. We find that RBD drives RNA -dependent phase separation but forms large and irregularly shaped droplets that are rescued by LCD in trans. Electrophoretic mobility shift assay (EMSA) and single -molecule fluorescence assays reveal that, while both LCD and RBD bind RNA, RBD drives RNA engagement and multivalent complex formation. While RBD alone exhibits delayed RNA recognition and a less dynamic RNP complex compared to full-length FUS, LCD in trans rescues full-length FUS activity. Likewise, cell -based data show RBD forms nucleolar condensates while LCD in trans rescues the diffuse nucleoplasm localization of fulllength FUS. Our results point to a regulatory role of LCD in tuning the RNP interaction and buffering phase separation.

引用

页码：177 / 187.e5

页数：17

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