Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390-9152, USA.
Cell. 2012 May 11;149(4):768-79. doi: 10.1016/j.cell.2012.04.016.
Cellular granules lacking boundary membranes harbor RNAs and their associated proteins and play diverse roles controlling the timing and location of protein synthesis. Formation of such granules was emulated by treatment of mouse brain extracts and human cell lysates with a biotinylated isoxazole (b-isox) chemical. Deep sequencing of the associated RNAs revealed an enrichment for mRNAs known to be recruited to neuronal granules used for dendritic transport and localized translation at synapses. Precipitated mRNAs contain extended 3' UTR sequences and an enrichment in binding sites for known granule-associated proteins. Hydrogels composed of the low complexity (LC) sequence domain of FUS recruited and retained the same mRNAs as were selectively precipitated by the b-isox chemical. Phosphorylation of the LC domain of FUS prevented hydrogel retention, offering a conceptual means of dynamic, signal-dependent control of RNA granule assembly.
无膜细胞颗粒包含 RNA 及其相关蛋白，在控制蛋白质合成的时间和位置方面发挥着多种作用。通过用生物素化异恶唑（b-isox）化学物质处理小鼠脑提取物和人细胞裂解物，可以模拟此类颗粒的形成。对相关 RNA 的深度测序显示，富含招募到用于树突运输和突触局部翻译的神经元颗粒中的 mRNA。沉淀的 mRNA 包含延伸的 3'UTR 序列和已知颗粒相关蛋白的结合位点富集。由 FUS 的低复杂度（LC）序列域组成的水凝胶募集并保留了与 b-isox 化学物质选择性沉淀的相同的 mRNA。FUS 的 LC 结构域的磷酸化阻止了水凝胶的保留，为 RNA 颗粒组装的动态、信号依赖性控制提供了一种概念上的方法。
