Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390-9152, USA.
Cell. 2012 May 11;149(4):753-67. doi: 10.1016/j.cell.2012.04.017.
Eukaryotic cells contain assemblies of RNAs and proteins termed RNA granules. Many proteins within these bodies contain KH or RRM RNA-binding domains as well as low complexity (LC) sequences of unknown function. We discovered that exposure of cell or tissue lysates to a biotinylated isoxazole (b-isox) chemical precipitated hundreds of RNA-binding proteins with significant overlap to the constituents of RNA granules. The LC sequences within these proteins are both necessary and sufficient for b-isox-mediated aggregation, and these domains can undergo a concentration-dependent phase transition to a hydrogel-like state in the absence of the chemical. X-ray diffraction and EM studies revealed the hydrogels to be composed of uniformly polymerized amyloid-like fibers. Unlike pathogenic fibers, the LC sequence-based polymers described here are dynamic and accommodate heterotypic polymerization. These observations offer a framework for understanding the function of LC sequences as well as an organizing principle for cellular structures that are not membrane bound.
真核细胞含有称为 RNA 颗粒的 RNA 和蛋白质的复合物。这些结构中的许多蛋白质都含有 KH 或 RRM RNA 结合域以及具有未知功能的低复杂度 (LC) 序列。我们发现，将细胞或组织裂解物暴露于生物素化异恶唑 (b-isox) 化学物质会沉淀数百种 RNA 结合蛋白，这些蛋白与 RNA 颗粒的组成成分有很大的重叠。这些蛋白质中的 LC 序列对于 b-isox 介导的聚集是必需且充分的，并且这些结构域可以在没有化学物质的情况下发生浓度依赖性的相转变，形成凝胶样状态。X 射线衍射和 EM 研究表明，水凝胶由均匀聚合的类淀粉样纤维组成。与致病性纤维不同，这里描述的基于 LC 序列的聚合物是动态的，并能容纳异质聚合。这些观察结果为理解 LC 序列的功能以及为非膜结合的细胞结构提供了一个组织原则。
