Abstract：
T-box riboswitches are widespread bacterial regulatory noncoding RNAs that directly interact with tRNAs and switch conformations to regulate the transcription or translation of genes related to amino acid metabolism. Recent studies in Bacilli have revealed the core mechanisms of T-boxes that enable multivalent, specific recognition of both the identity and aminoacylation status of the tRNA substrates. However, in-depth knowledge of a vast number of T-boxes in other bacterial species remains scarce, although a remarkable structural diversity particularly among pathogens, is apparent. In the present study, analysis of T-boxes that control the transcription of glycyl-tRNA synthetases from four prominent human pathogens revealed significant structural idiosyncrasies. Nonetheless, these diverse T-boxes maintain functional T-box:tRNAGly interactions both in vitro and in vivo. Probing analysis not only validated recent structural observations but also expanded our knowledge on the substantial diversities among T-boxes and suggest interesting distinctions from the canonical Bacilli T-boxes. Surprisingly, some glycyl T-boxes seem to redirect the T-box trajectory in the absence of recognizable K-turns or contain Stem II modules that are generally absent in glycyl T-boxes. These results consolidate the notion of lineage-specific diversification and elaboration of the T-box mechanism and corroborate the potential of T-boxes as promising species-specific RNA targets for next-generation antibacterial compounds.
摘要：
T-box核糖开关是广泛存在的细菌调节性非编码RNA,其直接与tRNA相互作用并转换构象以调节与氨基酸代谢相关的基因的转录或翻译。最近在芽孢杆菌的研究揭示了T盒的核心机制，使多价，tRNA底物的身份和氨基酰化状态的特异性识别。然而,对其他细菌物种中大量T盒的深入了解仍然很少，尽管结构差异显著，特别是在病原体之间，很明显。在本研究中,对控制来自四种主要人类病原体的甘氨酰-tRNA合成酶转录的T盒的分析揭示了显着的结构特性。尽管如此，这些不同的T-box在体外和体内都保持功能性T-box:tRNAGly相互作用。探测分析不仅验证了最近的结构观察结果，而且扩展了我们对T盒之间实质性差异的了解，并提出了与规范BacilliT盒的有趣区别。令人惊讶的是,在没有可识别的K转角的情况下，一些甘氨酰T盒似乎会重定向T盒的轨迹，或者包含甘氨酰T盒中通常不存在的茎II模块。这些结果巩固了谱系特异性多样化的概念和T-box机制的阐述，并证实了T-box作为下一代抗菌化合物的有希望的物种特异性RNA靶标的潜力。
