Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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Nosella, ML; Tereshchenko, M; Pritišanac, I; Chong, PA; Toretsky, JA; Lee, HO; Forman-Kay, JD.
O-Linked-N-Acetylglucosaminylation of the RNA-Binding Protein EWS N-Terminal Low Complexity Region Reduces Phase Separation and Enhances Condensate Dynamics.
J Am Chem Soc. 2021; 143(30):11520-11534
Doi: 10.1021/jacs.1c04194
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PubMed
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- Abstract:
- Many membraneless organelles are thought to be biomolecular condensates formed by phase separation of proteins and other biopolymers. Post-translational modifications (PTMs) can impact protein phase separation behavior, although for many PTMs this aspect of their function is unknown. O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is an abundant form of intracellular glycosylation whose roles in regulating biomolecular condensate assembly and dynamics have not been delineated. Using an in vitro approach, we found that O-GlcNAcylation reduces the phase separation propensity of the EWS N-terminal low complexity region (LCRN) under different conditions, including in the presence of the arginine- and glycine-rich RNA-binding domains (RBD). O-GlcNAcylation enhances fluorescence recovery after photobleaching (FRAP) within EWS LCRN condensates and causes the droplets to exhibit more liquid-like relaxation following fusion. Following extended incubation times, EWS LCRN+RBD condensates exhibit diminished FRAP, indicating a loss of fluidity, while condensates containing the O-GlcNAcylated LCRN do not. In HeLa cells, EWS is less O-GlcNAcylated following OGT knockdown, which correlates with its increased accumulation in a filter retardation assay. Relative to the human proteome, O-GlcNAcylated proteins are enriched with regions that are predicted to phase separate, suggesting a general role of O-GlcNAcylation in regulation of biomolecular condensates.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylglucosamine - chemistry, metabolism
- Biomolecular Condensates - administration & dosage
- HeLa Cells - administration & dosage
- Humans - administration & dosage
- Protein Domains - administration & dosage
- Protein Processing, Post-Translational - administration & dosage
- RNA-Binding Protein EWS - chemistry, metabolism
- Tumor Cells, Cultured - administration & dosage