ssrA标签及其变体在细菌蛋白质降解中的研究与应用进展

Study on ssrA Tag and its Variants Degradating Bacterial Protein

在原核生物的基因表达过程中,核裂解或转录错误等事件的存在往往使转录所得mRNA截短,即3′端缺少终止密码子。因此以截短型mRNA为模板的翻译过程会使核糖体停滞于3′端,这种mRNA缺少3′终止密码子导致核糖体停滞的突变被称为No-Go突变。为使核糖体循环顺利进行,兼具tRNA和mRNA功能的tmRNA将被募集发生在停滞的3′端,为停滞的新生多肽C端加载被称为ssrA标签的短肽标记并以自带的终止密码子终止肽链合成,释放核糖体。ssrA标签作为Degron(降解决定子)会引导多肽降解,以确保维持细胞的蛋白稳定与合成能力。由于ssrA标签具有靶向蛋白降解的能力,因此该标签在生物工程领域得到了广泛的开发和应用。文章总结了ssrA标签的种类,介导蛋白降解的机制和突变体,展望了ssrA标签在生物工程中的应用前景,以期为进一步开发靶向蛋白降解系统提供参考。

The occurring of nuclear cleavage or transcription errors lead to the transcribed mRNA truncated during prokaryotic gene expression,which results in the absence of stop codons at the 3′end of mRNA.This called NO⁃Go mutation stalls ribosomes at 3′end of the truncated mRNAs.To process the ribosome cycle proceed smoothly,the tmRNA which has both the tRNA and mRNA activities will be recruited at the stagnant 3′end,loading the stagnant nascent polypeptide C⁃terminal with a short peptide tag called the ssrA tag terminates synthesis with its own stop codon and releases the ribosome.The ssrA tag acts as a degron(degradation determinator)that guides peptide degradation to ensure the stability and ability of cytoproteins.The ssrA tag has been widely developed and applied in the field of bioengineering owing to its ability to degrading the target protein.To enlighten the further research and development of targeted protein degradation systems,this review summarizes the types of ssrA tags,the mechanisms and mutants that mediate protein degradation,and looks forward to the application prospects of ssrA tag in bioengineering,in order to provide a reference for the further.