Riboswitches sense specific cellular metabolites, leading to messenger RNA conformational changes that regulate downstream genes. Here we review the three known prequeosine1 (preQ1) riboswitch classes, which encompass five gene-regulatory motifs derived from distinct consensus models of folded RNA pseudoknots. Structural and functional analyses reveal multiple gene-regulation strategies ranging from partial occlusion of the ribosome-binding Shine-Dalgarno sequence (SDS), SDS sequestration driven by kinetic or thermodynamic folding pathways, direct preQ1 recognition by the SDS, and complete SDS burial in the riboswitch architecture. Family members can also induce elemental transcriptional pausing, which depends on ligand-mediated pseudoknot formation. Accordingly, preQ1 family members provide insight into a wide range of gene-regulatory tactics as well as a diverse repertoire of chemical approaches used to recognize the preQ1 metabolite. From a broader perspective, future challenges for the field will include the identification of new riboswitches in messenger RNAs that do not possess an SDS or those that induce ligand-dependent transcriptional pausing. When choosing an antibacterial target, the field must also consider how well a riboswitch accommodates mutations. Investigation of riboswitches in their natural context will also be critical to elucidate how RNA-mediated gene regulation influences organism fitness, thus providing a firm foundation for antibiotic development.

中文翻译：

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Knotty 很好：preQ1 核糖开关家族的代谢物结合和 RNA 介导的基因调控。


核糖开关感应特定的细胞代谢物，导致调节下游基因的信使 RNA 构象变化。在这里，我们回顾了三种已知的 prequeosine1 （preQ1） 核糖开关类别，它们包含来自折叠 RNA 假结的不同共有模型的五个基因调控基序。结构和功能分析揭示了多种基因调控策略，包括核糖体结合 Shine-Dalgarno 序列 （SDS） 的部分闭塞、动力学或热力学折叠途径驱动的 SDS 隔离、SDS 直接识别 preQ1 以及核糖开关结构中的 SDS 完全埋藏。家族成员还可以诱导元素转录暂停，这取决于配体介导的假结形成。因此，preQ1 家族成员提供了对各种基因调控策略以及用于识别 preQ1 代谢物的各种化学方法的见解。从更广泛的角度来看，该领域未来的挑战将包括在不具有 SDS 的信使 RNA 或诱导配体依赖性转录暂停的信使 RNA 中鉴定新的核糖开关。在选择抗菌靶点时，该领域还必须考虑核糖开关适应突变的能力。在自然环境中研究核糖开关对于阐明 RNA 介导的基因调控如何影响生物体适应性也至关重要，从而为抗生素开发提供坚实的基础。