Lin Yuan, Protter David S W, Rosen Michael K, Parker Roy
The HHMI Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
The HHMI Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA; Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Mol Cell. 2015 Oct 15;60(2):208-19. doi: 10.1016/j.molcel.2015.08.018. Epub 2015 Sep 24.
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.
真核细胞拥有众多动态的无膜细胞器——核糖核蛋白（RNP）颗粒，其富含RNA以及含有无序区域的RNA结合蛋白。我们证明，关键RNP颗粒组分的无序区域以及全长颗粒蛋白hnRNPA1能够在体外发生相分离，产生动态的液滴。低盐浓度或RNA可促进相分离。随着时间的推移，通过光漂白后荧光恢复减慢和耐盐性评估，这些液滴会成熟为更稳定的状态。成熟过程通常与纤维结构的形成同时发生。不同的无序结构域可以共同组装成相分离的液滴。这些生物物理特性证明了一种合理的机制，即无序区域之间的相互作用与RNA结合相结合，可通过促进相分离在体内有助于RNP颗粒的组装。从动态液体到稳定纤维的转变可能受到调控，以产生具有不同物理化学性质和功能的细胞结构。调控异常可能导致涉及异常RNA颗粒的疾病。
