Stress-dependent condensate formation regulated by the ubiquitin-related modifier Urm1

Cairo, Lucas V.; Hong, Xiaoyu; Müller, Martin B.D.; Yuste-Checa, Patricia; Jagadeesan, Chandhuru; Bracher, Andreas; Park, Sae-Hun; Hayer-Hartl, Manajit und Hartl, F. Ulrich (2024): Stress-dependent condensate formation regulated by the ubiquitin-related modifier Urm1. In: Cell, Bd. 187, Nr. 17, e28: S. 4656-4673

Abstract

The ability of proteins and RNA to coalesce into phase-separated assemblies, such as the nucleolus and stress granules, is a basic principle in organizing membraneless cellular compartments. While the constituents of biomolecular condensates are generally well documented, the mechanisms underlying their formation under stress are only partially understood. Here, we show in yeast that covalent modification with the ubiquitin-like modifier Urm1 promotes the phase separation of a wide range of proteins. We find that the drop in cellular pH induced by stress triggers Urm1 self-association and its interaction with both target proteins and the Urm1-conjugating enzyme Uba4. Urmylation of stress-sensitive proteins promotes their deposition into stress granules and nuclear condensates. Yeast cells lacking Urm1 exhibit condensate defects that manifest in reduced stress resilience. We propose that Urm1 acts as a reversible molecular “adhesive” to drive protective phase separation of functionally critical proteins under cellular stress.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > GenZentrum ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 00928674
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198