Institute for Systems Genetics, New York University Langone Medical Center, New York, NY, USA; Department of Biology, New York University, New York, NY, USA.
Institute for Systems Genetics, New York University Langone Medical Center, New York, NY, USA.
Mol Cell. 2024 Jul 25;84(14):2698-2716.e9. doi: 10.1016/j.molcel.2024.06.024.
The cell interior is packed with macromolecules of mesoscale size, and this crowded milieu significantly influences cellular physiology. Cellular stress responses almost universally lead to inhibition of translation, resulting in polysome collapse and release of mRNA. The released mRNA molecules condense with RNA-binding proteins to form ribonucleoprotein (RNP) condensates known as processing bodies and stress granules. Here, we show that polysome collapse and condensation of RNA transiently fluidize the cytoplasm, and coarse-grained molecular dynamic simulations support this as a minimal mechanism for the observed biophysical changes. Increased mesoscale diffusivity correlates with the efficient formation of quality control bodies (Q-bodies), membraneless organelles that compartmentalize misfolded peptides during stress. Synthetic, light-induced RNA condensation also fluidizes the cytoplasm. Together, our study reveals a functional role for stress-induced translation inhibition and formation of RNP condensates in modulating the physical properties of the cytoplasm to enable efficient response of cells to stress conditions.
细胞内部充满了中尺度大小的生物大分子，这种拥挤的环境显著影响着细胞的生理学。细胞应激反应几乎普遍导致翻译抑制，导致多核糖体崩溃和 mRNA 释放。释放的 mRNA 分子与 RNA 结合蛋白凝聚形成核糖核蛋白 (RNP) 凝聚物，称为处理体和应激颗粒。在这里，我们表明多核糖体崩溃和 RNA 凝聚使细胞质短暂地流动化，粗粒度分子动力学模拟支持这是观察到的生物物理变化的最小机制。中尺度扩散性的增加与质量控制体 (Q-体) 的有效形成相关，Q-体是在应激过程中分隔错误折叠肽的无膜细胞器。合成的、光诱导的 RNA 凝聚也使细胞质流动化。总之，我们的研究揭示了应激诱导的翻译抑制和 RNP 凝聚形成在调节细胞质物理性质方面的功能作用，从而使细胞能够有效地应对应激条件。
