Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins.
Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins.
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DOI：
10.1016/j.molcel.2015.08.018
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发表时间：
2015-10-15
期刊：
影响因子：
16
通讯作者：
Parker R
中科院分区：
文献类型：
--
作者：
Lin Y;Protter DS;Rosen MK;Parker R
真核细胞具有许多动态的无膜细胞器，RNP颗粒，富含RNA和RNA结合蛋白，含有无序区域。我们证明，RNP关键颗粒成分的无序区域和全长颗粒蛋白hnRNPA 1可以在体外进行相分离，产生动态液滴。低盐浓度或RNA促进相分离。随着时间的推移，液滴成熟到更稳定的状态，如通过光漂白和耐盐性后缓慢的荧光恢复所评估的。成熟通常与纤维结构的形成一致。不同的无序结构域可以共组装成相分离的液滴。这些生物物理特性表明了一种合理的机制，通过这种机制，无序区域之间的相互作用，再加上RNA结合，可以通过促进相分离促进RNP颗粒在体内组装。可以调节从动态液体到稳定纤维的进展，以产生具有不同理化性质和功能的细胞结构。错误调节可能导致涉及异常RNA颗粒的疾病。
Eukaryotic cells possess numerous dynamic membrane-less organelles, RNP granules, enriched in RNA and RNA binding proteins containing disordered regions. We demonstrate that the disordered regions of key RNP granule components, and the full-length granule protein hnRNPA1, can phase separate in vitro, producing dynamic liquid droplets. Phase separation is promoted by low salt concentrations or RNA. Over time, the droplets mature to more stable states, as assessed by slowed fluorescence recovery after photobleaching and resistance to salt. Maturation often coincides with formation of fibrous structures. Different disordered domains can co-assemble into phase-separated droplets. These biophysical properties demonstrate a plausible mechanism by which interactions between disordered regions, coupled with RNA binding, could contribute to RNP granule assembly in vivo through promoting phase separation. Progression from dynamic liquids to stable fibers may be regulated to produce cellular structures with diverse physiochemical properties and functions. Misregulation could contribute to diseases involving aberrant RNA granules.