摘要

抗生素抗性基因通常由复杂的机制调节，所述机制在响应抗生素暴露时激活基因表达。越来越多的证据表明，顺式作用的非编码RNA在调节许多抗性基因的表达中发挥主要作用，特别是那些抵消翻译抑制抗生素的作用的基因。这些ncRNA位于调控基因的5'UTR中，并通过将翻译的核糖体募集到嵌入ncRNA的短上游开放阅读框（uORF）中来感知抗生素的存在。在存在翻译抑制性抗生素的情况下，核糖体会阻止uORF，改变调节子的RNA结构并将抗性基因的表达切换为“ON”。根据相应uORF的长度和组成，这些核糖调节剂的特异性被调整为特定类型的抗生素。在这里，我们回顾了最近的工作，描述了新型抗生素感应RNA为基础的监管机构，阐明了它们在细菌中控制抗生素耐药性的分子机制。

Antibiotic resistance genes are commonly regulated by sophisticated mechanisms that activate gene expression in response to antibiotic exposure. Growing evidence suggest that cis-acting non-coding RNAs play a major role in regulating the expression of many resistance genes, specifically those which counteract the effects of translation-inhibiting antibiotics. These ncRNAs reside in the 5′UTR of the regulated gene, and sense the presence of the antibiotics by recruiting translating ribosomes onto short upstream open reading frames (uORFs) embedded in the ncRNA. In the presence of translation-inhibiting antibiotics ribosomes arrest over the uORF, altering the RNA structure of the regulator and switching the expression of the resistance gene to ‘ON’. The specificity of these riboregulators is tuned to sense-specific classes of antibiotics based on the length and composition of the respective uORF. Here we review recent work describing new types of antibiotic-sensing RNA-based regulators and elucidating the molecular mechanisms by which they function to control antibiotic resistance in bacteria.

https://www.sciencedirect.com/science/article/pii/S1369527416301503