Abstract:
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.
摘要:
细胞内部充满了中尺度大小的大分子,这个拥挤的环境会显著影响细胞生理学。细胞应激反应几乎普遍导致翻译的抑制,导致多聚体塌陷和mRNA释放。释放的mRNA分子与RNA结合蛋白缩合,形成核糖核蛋白(RNP)缩合物,称为加工体和应激颗粒。这里,我们表明RNA的多聚体崩溃和凝聚暂时流化了细胞质,和粗粒度的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。增加的中尺度扩散率与质量控制体(Q体)的有效形成相关,在应激期间分隔错误折叠肽的无膜细胞器。合成,光诱导的RNA缩合也使细胞质流化。一起,我们的研究揭示了应激诱导的翻译抑制和RNP缩合物形成在调节细胞质的物理性质以使细胞对应激条件的有效反应中的功能作用。