Wellcome Centre for Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford. OX3 7BN, UK.
Cells. 2020 Mar 7;9(3):650. doi: 10.3390/cells9030650.
Mechanical forces acting on biological systems, at both the macroscopic and microscopic levels, play an important part in shaping cellular phenotypes. There is a growing realization that biomolecules that respond to force directly applied to them, or via mechano-sensitive signalling pathways, can produce profound changes to not only transcriptional pathways, but also in protein translation. Forces naturally occurring at the molecular level can impact the rate at which the bacterial ribosome translates messenger RNA (mRNA) transcripts and influence processes such as co-translational folding of a nascent protein as it exits the ribosome. In eukaryotes, force can also be transduced at the cellular level by the cytoskeleton, the cell's internal filamentous network. The cytoskeleton closely associates with components of the translational machinery such as ribosomes and elongation factors and, as such, is a crucial determinant of localized protein translation. In this review we will give (1) a brief overview of protein translation in bacteria and eukaryotes and then discuss (2) how mechanical forces are directly involved with ribosomes during active protein synthesis and (3) how eukaryotic ribosomes and other protein translation machinery intimately associates with the mechanosensitive cytoskeleton network.
机械力在生物系统中发挥着重要作用,无论是在宏观还是微观水平上,都会影响细胞表型的形成。人们越来越认识到,直接作用于生物分子或通过机械敏感信号通路的生物分子可以产生深远的变化,不仅影响转录途径,还影响蛋白质翻译。在分子水平上自然产生的力会影响细菌核糖体翻译信使 RNA(mRNA)转录本的速度,并影响新生蛋白质从核糖体中出口时的共翻译折叠等过程。在真核生物中,细胞骨架也可以在细胞水平上传递力,细胞骨架是细胞内部的丝状网络。细胞骨架与核糖体和延伸因子等翻译机制的组成部分密切相关,因此是局部蛋白质翻译的关键决定因素。在这篇综述中,我们将简要概述细菌和真核生物中的蛋白质翻译,然后讨论(1)机械力如何在蛋白质合成过程中直接与核糖体相互作用,以及(2)真核核糖体和其他蛋白质翻译机制如何与机械敏感的细胞骨架网络密切相关。