Department of Biochemistry, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Int J Mol Sci. 2022 Mar 26;23(7):3624. doi: 10.3390/ijms23073624.
Eukaryotic cells react to various stress conditions with the rapid formation of membrane-less organelles called stress granules (SGs). SGs form by multivalent interactions between RNAs and RNA-binding proteins and are believed to protect stalled translation initiation complexes from stress-induced degradation. SGs contain hundreds of different mRNAs and proteins, and their assembly and disassembly are tightly controlled by post-translational modifications. The ubiquitin system, which mediates the covalent modification of target proteins with the small protein ubiquitin ('ubiquitylation'), has been implicated in different aspects of SG metabolism, but specific functions in SG turnover have only recently emerged. Here, we summarize the evidence for the presence of ubiquitylated proteins at SGs, review the functions of different components of the ubiquitin system in SG formation and clearance, and discuss the link between perturbed SG clearance and the pathogenesis of neurodegenerative disorders. We conclude that the ubiquitin system plays an important, medically relevant role in SG biology.
真核细胞会对各种应激条件做出反应，迅速形成无膜细胞器，称为应激颗粒 (SGs)。SGs 通过 RNA 和 RNA 结合蛋白之间的多价相互作用形成，据信可以保护停滞的翻译起始复合物免受应激诱导的降解。SGs 包含数百种不同的 mRNA 和蛋白质，其组装和拆卸受到翻译后修饰的严格控制。泛素系统介导靶蛋白与小分子蛋白泛素（“泛素化”）的共价修饰，已涉及 SG 代谢的不同方面，但在 SG 周转中的具体功能最近才出现。在这里，我们总结了 SG 中存在泛素化蛋白的证据，回顾了泛素系统不同成分在 SG 形成和清除中的功能，并讨论了 SG 清除失调与神经退行性疾病发病机制之间的联系。我们得出结论，泛素系统在 SG 生物学中具有重要的、与医学相关的作用。
