Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9152, USA; email:
Annu Rev Biochem. 2018 Jun 20;87:351-390. doi: 10.1146/annurev-biochem-061516-044700. Epub 2017 Dec 1.
In this review, we describe speculative ideas and early stage research concerning the flow of genetic information from the nuclear residence of genes to the disparate, cytoplasmic sites of protein synthesis. We propose that this process of information transfer is meticulously guided by transient structures formed from protein segments of low sequence complexity/intrinsic disorder. These low complexity domains are ubiquitously associated with regulatory proteins that control gene expression and RNA biogenesis, but they are also found in the central channel of nuclear pores, the nexus points of intermediate filament assembly, and the locations of action of other well-studied cellular proteins and pathways. Upon being organized into localized cellular positions via mechanisms utilizing properly folded protein domains, thereby facilitating elevated local concentration, certain low complexity domains adopt cross-β interactions that are both structurally specific and labile to disassembly. These weakly tethered assemblies, we propose, are built to relay the passage of genetic information from one site to another within a cell, ensuring that the process is of extreme fidelity.
在这篇综述中,我们描述了有关遗传信息从基因的核驻留位置流向蛋白质合成的不同细胞质位置的推测性想法和早期研究。我们提出,这个信息传递过程是由低序列复杂性/内在无序的蛋白质片段形成的瞬态结构精心指导的。这些低复杂度结构域普遍存在于调节基因表达和 RNA 生物发生的调控蛋白中,但也存在于核孔的中央通道、中间丝组装的连接点以及其他研究充分的细胞蛋白和途径的作用部位。通过利用正确折叠的蛋白质结构域来组织成局部细胞位置的机制,从而促进局部浓度的升高,某些低复杂度结构域采用交叉-β相互作用,这种相互作用具有结构特异性和易于解组装的特点。我们提出,这些弱连接的组装体是为了在细胞内从一个位置到另一个位置传递遗传信息而构建的,以确保该过程具有极高的保真度。