Palma Martine, Lejeune Fabrice
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 - U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.
Biol Rev Camb Philos Soc. 2021 Feb;96(1):310-329. doi: 10.1111/brv.12657. Epub 2020 Oct 22.
Recognition of the stop codon by the translation machinery is essential to terminating translation at the right position and to synthesizing a protein of the correct size. Under certain conditions, the stop codon can be recognized as a coding codon promoting translation, which then terminates at a later stop codon. This event, called stop codon readthrough, occurs either by error, due to a dedicated regulatory environment leading to generation of different protein isoforms, or through the action of a readthrough compound. This review focuses on the mechanisms of stop codon readthrough, the nucleotide and protein environments that facilitate or inhibit it, and the therapeutic interest of stop codon readthrough in the treatment of genetic diseases caused by nonsense mutations.
翻译机制对终止密码子的识别对于在正确位置终止翻译以及合成正确大小的蛋白质至关重要。在某些情况下，终止密码子可被识别为促进翻译的编码密码子，然后在随后的终止密码子处终止。这种事件称为终止密码子通读，它要么是由于错误发生，要么是由于导致产生不同蛋白质异构体的特定调节环境，或者是通过通读化合物的作用而发生。本综述重点关注终止密码子通读的机制、促进或抑制它的核苷酸和蛋白质环境，以及终止密码子通读在治疗由无义突变引起的遗传疾病方面的治疗意义。
