Distinct Features of Stress Granule Proteins Predict Localization in Membraneless Organelles. Issue 7 (27th March 2020)

• Record Type: Journal Article
• Authors: Kuechler, Erich R.; Budzyńska, Paulina M.; Bernardini, Jonathan P.; Gsponer, Jörg; Mayor, Thibault
• Is Part Of: Journal of molecular biology. Volume 432:Issue 7(2020)
• Page Start: 2349
• Page End: 2368
• Publication Date: 2020-03-27
• Subjects: liquid-liquid phase separation -- stress granules -- intrinsic protein disorder -- biomolecular condensates; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.02.020
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Recently generated proteomic data provides unprecedented insight into stress granule composition and stands as fruitful ground for further analysis. Stress granules are stress-induced biological assemblies that are of keen interest due to being linked to both long-term cell viability and a variety of protein aggregation-based diseases. Herein, we compile recently published stress granule composition data, formed specifically through heat and oxidative stress, for both mammalian ( Homo sapiens ) and yeast ( Saccharomyces cerevisiae ) cells. Interrogation of the data reveals that stress granule proteins are enriched in features that favor protein liquid-liquid phase separation, being highly disordered, soluble, and abundant while maintaining a high level of protein-protein interactions under basal conditions. Furthermore, these "stress granuleomes" are shown to be enriched for multidomained, RNA-binding proteins with increased potential for post-translational modifications. Findings are consistent with the notion that stress granule formation is driven by protein liquid-liquid phase separation. Furthermore, stress granule proteins appear poised near solubility limits while possessing the ability to dynamically alter their phase behavior in response to external threat. Interestingly, several features, such as protein disorder, are more prominent among stress granule proteins that share homologs between yeast and mammalian systems also found within stress-induced foci. We culminate results from our stress granule analysis into novel predictors for granule incorporation and validate the mammalian predictor's performance against multiple types of membraneless condensates and by colocalization microscopy. Graphical abstract: Image 1 Highlights: Stress granule proteins are enriched in specific features. Some features are distinct between yeast and human stress granule proteins. Yeast stress granules proteins conserved in human granules are more disordered. The mammalian granule z-score predicts localization of mammalian proteins into biological condensates.