摘要
蛋白质在核糖体的合成受多个分子层面的精细调控,包括核糖体停靠(ribosome stalling,亦称为核糖体延宕)机制,即核糖体可与tRNA及氨基酸、肽或其它化合物如抗生素持久结合形成复合物,使核糖体停靠在正在转录的前导肽mRNA的开放阅读框内,并促使前导肽下游未翻译结构基因如耐药基因mRNA的表达。核糖体停靠需要前导肽参与,可分为非抗生素依赖和抗生素依赖两种类型,后者诱导多种作用于核糖体靶位抗生素(如大环内酯类、氯霉素类及四环素类等)的耐药性形成。对大环内酯类介导的核糖体停靠已有深入了解,这些研究有助于了解抗生素耐药机制及进化,并从干扰蛋白质表达的角度探索控制耐药性和研发新型抗菌化合物。本文也讨论了影响蛋白质表达的核糖体拯救(ribosme rescue)和核糖开关(riboswitch)机制。
Ribosome-mediated protein synthesis is rigorously regulated at various molecular levels, including he mechanisms of ribosome stalling, a phenomenon where ribosome, tRNA, amino acids, nascent （leader） peptides md/or compounds such as antibiotics can together form so-called stalled ribosomal complex that arrests the ongoing iynthesis of the nascent peptides and allows the structural changes of the secondary mRNA, resulting in the increased ranslation of the downstream structural genes such as resistance genes. While requiring the involvement of nascent ieptides, ribosome stalling can be divided into at least two types, either antibiotic-independent or antibiotic-dependent. [he latter plays an important role in inducible resistance to antibiotics targeting ribosome such as macrolides, unpheniols and tetracyclines. There is currently in-depth understanding of macrolide-mediated ribosome stalling and he relevant advances can facilitate the illustration of resistance mechanisms and evolution as well as the development if the novel antibacterial agents. In addition, discussions are made on ribosome rescue and riboswitch that also nftuence protein expressions.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2014年第3期161-170,共10页
Chinese Journal of Antibiotics
基金
国家自然科学基金委项目(81373454)
四川省科技厅重点科技项目(2013jy0065)
