MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Int J Biol Macromol. 2024 Oct;277(Pt 3):134411. doi: 10.1016/j.ijbiomac.2024.134411. Epub 2024 Aug 2.
Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs. However, the role of this writer-reader system in SG assembly remains unclear. Here, we found that PRMT1 methylates SG constituent RNA-binding proteins (RBPs) on their RGG motifs. Besides, we report that TDRD3, as a reader of asymmetric dimethylarginines, enhances RNA binding to recruit additional RNAs and RBPs, lowering the percolation threshold and promoting SG assembly. Our study enriches our understanding of the molecular mechanism of SG formation by elucidating the functions of PRMT1 and TDRD3. We anticipate that our study will provide a new perspective for comprehensively understanding the functions of PTMs in liquid-liquid phase separation driven condensate assembly.
应激颗粒（SGs）是一种无膜细胞器（MLOs）或细胞质隔室，在暴露于环境细胞应激诱导刺激时形成。SGs 基于一组细胞质蛋白和 mRNA 的核糖核蛋白复合物，由于细胞应激诱导的多核糖体解体而在翻译过程中受阻。翻译后修饰（PTMs）如甲基化参与 SG 的组装，甲基转移酶 PRMT1 及其阅读器 TDRD3 共定位于 SG 中。然而，这个写入器-读取器系统在 SG 组装中的作用尚不清楚。在这里，我们发现 PRMT1 在其 RGG 基序上甲基化 SG 组成蛋白的 RNA 结合蛋白（RBPs）。此外，我们报告说，作为不对称二甲基精氨酸的读取器，TDRD3 增强 RNA 结合以招募更多的 RNA 和 RBPs，降低渗透阈值并促进 SG 组装。我们的研究通过阐明 PRMT1 和 TDRD3 的功能，丰富了我们对 SG 形成的分子机制的理解。我们预计，我们的研究将为全面理解 PTMs 在液-液相分离驱动凝聚物组装中的功能提供新的视角。
