1] MRC Laboratory of Molecular Biology, Cambridge, UK. [2] Present address: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Nat Struct Mol Biol. 2014 Sep;21(9):833-9. doi: 10.1038/nsmb.2876. Epub 2014 Aug 24.
Although many proteins are localized after translation, asymmetric protein distribution is also achieved by translation after mRNA localization. Why are certain mRNA transported to a distal location and translated on-site? Here we undertake a systematic, genome-scale study of asymmetrically distributed protein and mRNA in mammalian cells. Our findings suggest that asymmetric protein distribution by mRNA localization enhances interaction fidelity and signaling sensitivity. Proteins synthesized at distal locations frequently contain intrinsically disordered segments. These regions are generally rich in assembly-promoting modules and are often regulated by post-translational modifications. Such proteins are tightly regulated but display distinct temporal dynamics upon stimulation with growth factors. Thus, proteins synthesized on-site may rapidly alter proteome composition and act as dynamically regulated scaffolds to promote the formation of reversible cellular assemblies. Our observations are consistent across multiple mammalian species, cell types and developmental stages, suggesting that localized translation is a recurring feature of cell signaling and regulation.
虽然许多蛋白质是在翻译后定位的，但 mRNA 定位后的翻译也可以实现蛋白质的不对称分布。为什么某些 mRNA 会被运送到远端位置并在原位翻译呢？在这里，我们对哺乳动物细胞中不对称分布的蛋白质和 mRNA 进行了系统的、全基因组规模的研究。我们的研究结果表明，通过 mRNA 定位实现的不对称蛋白质分布可以提高相互作用的保真度和信号敏感性。在远端位置合成的蛋白质通常含有内在无序的片段。这些区域通常富含促进组装的模块，并且经常受到翻译后修饰的调节。这些蛋白质受到严格的调控，但在受到生长因子刺激时表现出明显不同的时间动态。因此，在原位合成的蛋白质可以快速改变蛋白质组的组成，并作为动态调节的支架，促进可逆细胞组装的形成。我们的观察结果在多种哺乳动物物种、细胞类型和发育阶段都是一致的，这表明局部翻译是细胞信号转导和调控的一个反复出现的特征。
