德国马克斯·普朗克生物化学研究所F. Ulrich Hartl，Manajit Hayer-Hartl和Sae-Hun Park共同合作，近期取得重要工作进展。他们研究提出了由泛素相关修饰物Urm1调节的应力依赖性凝结物形成的观点。相关研究成果2024年6月27日在线发表于《细胞》杂志上。

据介绍，蛋白质和RNA结合成相分离的组装体（如核仁和应激颗粒）的能力是组织无膜细胞区室的基本原理。虽然生物分子凝聚物的成分已经被很好的报道了，但它们在应激压力下形成的机制并不完全清楚。

研究人员在酵母中发现，用泛素样修饰剂Urm1进行共价修饰可以促进多种蛋白质的相分离。应激诱导的细胞pH值下降触发了Urm1自结合及其与靶蛋白和Urm1结合酶Uba4的相互作用。应激敏感蛋白的氨酰化促进它们沉积到应激颗粒和核凝聚物中。缺乏Urm1的酵母细胞表现出凝结缺陷，表现为应激恢复能力降低。

总之，研究人员提出，Urm1作为一种可逆的分子“粘合剂”，在细胞应激下驱动功能关键蛋白的保护性相分离。

附：英文原文

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

Author: Lucas V. Cairo, Xiaoyu Hong, Martin B.D. Müller, Patricia Yuste-Checa, Chandhuru Jagadeesan, Andreas Bracher, Sae-Hun Park, Manajit Hayer-Hartl, F. Ulrich Hartl

Issue&Volume: 2024-06-27

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.

DOI: 10.1016/j.cell.2024.06.009

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00649-4