Nørholm Morten H H, Light Sara, Virkki Minttu T I, Elofsson Arne, von Heijne Gunnar, Daley Daniel O
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91, Sweden.
Biochim Biophys Acta. 2012 Apr;1818(4):1091-6. doi: 10.1016/j.bbamem.2011.08.018. Epub 2011 Aug 22.
With synthetic gene services, molecular cloning is as easy as ordering a pizza. However choosing the right RNA code for efficient protein production is less straightforward, more akin to deciding on the pizza toppings. The possibility to choose synonymous codons in the gene sequence has ignited a discussion that dates back 50 years: Does synonymous codon use matter? Recent studies indicate that replacement of particular codons for synonymous codons can improve expression in homologous or heterologous hosts, however it is not always successful. Furthermore it is increasingly apparent that membrane protein biogenesis can be codon-sensitive. Single synonymous codon substitutions can influence mRNA stability, mRNA structure, translational initiation, translational elongation and even protein folding. Synonymous codon substitutions therefore need to be carefully evaluated when membrane proteins are engineered for higher production levels and further studies are needed to fully understand how to select the codons that are optimal for higher production. This article is part of a Special Issue entitled: Protein Folding in Membranes.
借助合成基因服务，分子克隆就像订购披萨一样简单。然而，选择合适的RNA编码以实现高效蛋白质生产并非那么直接，更类似于决定披萨的配料。在基因序列中选择同义密码子的可能性引发了一场可以追溯到50年前的讨论：同义密码子的使用重要吗？最近的研究表明，用同义密码子替换特定密码子可以提高在同源或异源宿主中的表达，但并非总是成功。此外，越来越明显的是，膜蛋白生物合成可能对密码子敏感。单个同义密码子替换可以影响mRNA稳定性、mRNA结构、翻译起始、翻译延伸，甚至蛋白质折叠。因此，当为提高产量而对膜蛋白进行工程改造时，需要仔细评估同义密码子替换，并且需要进一步研究以充分了解如何选择最适合提高产量的密码子。本文是名为：膜中的蛋白质折叠的特刊的一部分。
