细菌应激颗粒通过排除核糖核酸酶保护mRNA
Bacterial stress granule protects mRNA through ribonucleases exclusion
AI总结：
本研究揭示细菌应激颗粒通过长度依赖的相分离选择mRNA，并利用表面电荷排斥核糖核酸酶，从而保护mRNA免受降解，并在应激解除后促进翻译，增强细胞适应性。
摘要：
通过液-液相分离（LLPS）形成的无膜液滴在mRNA储存中发挥关键作用，使生物体能够迅速响应环境变化。然而，mRNA在液滴内的整合与保护机制仍不清楚。在此，我们揭示了细菌聚集体（aggresomes）作为应激颗粒（SGs）在应激期间保护mRNA的作用。我们发现，应激发生时，可移动的mRNA分子基于长度依赖的焓增益超过熵损失，选择性地整合到单个蛋白质性应激颗粒中。随着应激持续，应激颗粒通过更强的非特异性RNA-蛋白质相互作用促进压实，从而促进较短RNA链的招募。值得注意的是，由于蛋白质表面电荷的影响，mRNA核糖核酸酶被排斥在细菌应激颗粒之外。这种排斥机制确保了应激条件下mRNA在应激颗粒内的完整性和保存，解释了mRNA如何被储存并免受降解。应激解除后，应激颗粒促进mRNA翻译，从而增强细胞在变化环境中的适应性。这些液滴在储存期间维持mRNA的生理活性，使其成为mRNA治疗药物生产的一个有趣的新候选方案。
英文摘要：
Membraneless droplets formed through liquid-liquid phase separation (LLPS) play a crucial role in mRNA storage, enabling organisms to swiftly respond to environmental changes. However, the mechanisms underlying mRNA integration and protection within droplets remain unclear. Here, we unravel the role of bacterial aggresomes as stress granules (SGs) in safeguarding mRNA during stress. We discovered that upon stress onset, mobile mRNA molecules selectively incorporate into individual proteinaceous SGs based on length-dependent enthalpic gain over entropic loss. As stress prolongs, SGs undergo compaction facilitated by stronger non-specific RNA-protein interactions, thereby promoting recruitment of shorter RNA chains. Remarkably, mRNA ribonucleases are repelled from bacterial SGs, due to the influence of protein surface charge. This exclusion mechanism ensures the integrity and preservation of mRNA within SGs during stress conditions, explaining how mRNA can be stored and protected from degradation. Following stress removal, SGs facilitate mRNA translation, thereby enhancing cell fitness in changing environments. These droplets maintain mRNA physiological activity during storage, making them an intriguing new candidate for mRNA therapeutics manufacturing.
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