Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response.
Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response.
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DOI：
10.1016/j.cell.2017.02.027
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发表时间：
2017-03-09
期刊：
影响因子：
64.5
通讯作者：
Drummond DA
中科院分区：
文献类型：
--
作者：
Riback JA;Katanski CD;Kear-Scott JL;Pilipenko EV;Rojek AE;Sosnick TR;Drummond DA
在真核细胞中，不同的应力触发RNA结合蛋白聚结成应力颗粒。在体外，应力颗粒相关蛋白可以分层形成液体，水凝胶，和其他组件缺乏固定的化学计量。观察这些现象通常需要远离生理压力的条件。我们表明，聚（A）结合蛋白（Pab 1在酵母），一个定义标记的压力颗粒，相分离，并形成水凝胶在体外暴露于生理应激条件下。其他RNA结合蛋白依赖于低复杂性区域（LCR）或RNA的相分离，而Pab1的LCR是不需要分层，RNA抑制it.Based上独特的进化模式，我们创建LCR突变系统地调整其生物物理特性和Pab1相分离在体外和体内。阻碍相分离的突变会降低生物体在长期压力下的适应性。因此，聚（A）结合蛋白作为一个生理压力传感器，利用相分离，以精确地标记应力发作，一个广泛的推广机制。
In eukaryotic cells, diverse stresses trigger coalescence of RNA-binding proteins into stress granules. In vitro, stress-granule-associated proteins can demix to form liquids, hydrogels, and other assemblies lacking fixed stoichiometry. Observing these phenomena has generally required conditions far removed from physiological stresses. We show that poly(A)-binding protein (Pab1 in yeast), a defining marker of stress granules, phase-separates and forms hydrogels in vitro upon exposure to physiological stress conditions. Other RNA-binding proteins depend upon low-complexity regions (LCRs) or RNA for phase separation, whereas Pab1’s LCR is not required for demixing, and RNA inhibits it. Based on unique evolutionary patterns, we create LCR mutations which systematically tune its biophysical properties and Pab1 phase separation in vitro and in vivo. Mutations which impede phase separation reduce organism fitness during prolonged stress. Poly(A)-binding protein thus acts as a physiological stress sensor, exploiting phase separation to precisely mark stress onset, a broadly generalizable mechanism.