Department of Life Sciences and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, PO Box 653, Beer-Sheva 8410501, Israel.
Department of Life Sciences and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, PO Box 653, Beer-Sheva 8410501, Israel.
Curr Opin Chem Biol. 2018 Oct;46:146-155. doi: 10.1016/j.cbpa.2018.07.012. Epub 2018 Jul 29.
Genetic code expansion enables the incorporation of unnatural amino acids into proteins thereby augmenting their physical and chemical properties. This is achieved by the reassignment of codons from their original sense to incorporate unnatural amino acids. The most commonly used methodology is stop codon suppression, which has resulted in numerous successful studies and applications in recent years. In these studies, many observations have been accumulated indicating that stop codon suppression efficiency depends on various cellular, operon and mRNA context effects. Predominant among these are mRNA context effects: the location of the stop codon along the mRNA governs, to a large extent, the efficiency and ability to successfully incorporate unnatural amino acids. Albeit their prevalence and importance, the mechanisms that govern context effects remain largely unknown. Herein, we will review what is known and yet to be understood with the intent to advance the propagation of genetic code expansion technology and to stimulate systematic research and debate of this open question.
遗传密码扩展使非天然氨基酸能够被掺入蛋白质中，从而增强它们的物理和化学性质。这是通过将密码子从它们的原始意义重新分配来掺入非天然氨基酸来实现的。最常用的方法是终止密码子抑制，近年来已在许多成功的研究和应用中得到应用。在这些研究中，积累了许多观察结果表明，终止密码子抑制效率取决于各种细胞、操纵子和 mRNA 上下文效应。其中主要的是 mRNA 上下文效应：终止密码子在 mRNA 上的位置在很大程度上决定了非天然氨基酸的掺入效率和能力。尽管它们普遍存在且很重要，但控制上下文效应的机制在很大程度上仍然未知。在这里，我们将回顾已知的和尚未理解的内容，旨在推进遗传密码扩展技术的传播，并激发对这个悬而未决的问题的系统研究和辩论。
