Dar Daniel, Sorek Rotem
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Curr Opin Microbiol. 2017 Apr;36:111-117. doi: 10.1016/j.mib.2017.02.005. Epub 2017 Apr 14.
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.
抗生素抗性基因通常受复杂机制调控,这些机制会在暴露于抗生素时激活基因表达。越来越多的证据表明,顺式作用非编码RNA在调控许多抗性基因的表达中起主要作用,特别是那些对抗翻译抑制性抗生素作用的基因。这些非编码RNA位于受调控基因的5'UTR中,并通过将正在翻译的核糖体招募到嵌入非编码RNA中的短上游开放阅读框(uORF)上来感知抗生素的存在。在存在翻译抑制性抗生素的情况下,核糖体在uORF上停滞,改变调节因子的RNA结构,并将抗性基因的表达切换为“开启”状态。这些核糖调节因子的特异性根据各自uORF的长度和组成,针对特定类别的抗生素进行调节。在此,我们综述了近期的研究工作,这些工作描述了新型基于RNA的抗生素感应调节因子,并阐明了它们在控制细菌抗生素抗性中发挥作用的分子机制。