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The roles of FUS-RNA binding domain and low complexity domain in RNA-dependent phase separation.
Ganser, Laura R; Niaki, Amirhossein Ghanbari; Yuan, Xincheng; Huang, Ethan; Deng, Dahlia; Djaja, Nathalie A; Ge, Yingda; Craig, Alanna; Langlois, Olivia; Myong, Sua.
Afiliação
  • Ganser LR; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Niaki AG; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Yuan X; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA; Program in Cell, Molecular, Developmental Biology, and Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA; Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21
  • Huang E; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Deng D; Program in Cell, Molecular, Developmental Biology, and Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA; Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA.
  • Djaja NA; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA; Program in Cell, Molecular, Developmental Biology, and Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA; Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21
  • Ge Y; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Craig A; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Langlois O; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Myong S; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA; Program in Cell, Molecular, Developmental Biology, and Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA; Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21
Structure ; 32(2): 177-187.e5, 2024 Feb 01.
Article em En | MEDLINE | ID: mdl-38070499
ABSTRACT
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 full-length FUS. Our results point to a regulatory role of LCD in tuning the RNP interaction and buffering phase separation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA / Proteína FUS de Ligação a RNA / Motivos de Ligação ao RNA / Separação de Fases Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA / Proteína FUS de Ligação a RNA / Motivos de Ligação ao RNA / Separação de Fases Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article