Tuning a riboswitch response through structural extension of a pseudoknot
Tuning a riboswitch response through structural extension of a pseudoknot
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DOI：
10.1073/pnas.1304585110
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发表时间：
2013-08-27
影响因子：
11.1
通讯作者：
Micura, Ronald
中科院分区：
文献类型：
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作者：
Souliere, Marie F.;Altman, Roger B.;Micura, Ronald
RNA折叠景观的结构和动态特征代表了细胞中RNA功能的关键方面，并且对于核糖开关介导的基因表达控制特别重要。在这里，利用单分子荧光能量转移成像，我们探索了preQ(1)II类核糖开关的折叠动力学，这是一种上游mRNA元件，调节下游编码的队列糖生物合成修饰酶。由于目前尚不清楚的原因，该系统的经典伪结折叠在其紧靠Shine-Dalgarno序列上游的3‘末端区域中含有额外的茎环结构，这有助于形成配体结合态。通过从多个结构角度对配体依赖的preQ(1)核糖开关折叠进行成像，我们揭示了额外的茎环强烈影响假结动力学，降低了其自发折叠的倾向，并增加了其对配体结合的反应性。我们的结论是，额外的茎环敏化了这个RNA，从而扩大了开/关调节开关的动态范围。
Structural and dynamic features of RNA folding landscapes represent critical aspects of RNA function in the cell and are particularly central to riboswitch-mediated control of gene expression. Here, using single-molecule fluorescence energy transfer imaging, we explore the folding dynamics of the preQ(1) class II riboswitch, an upstream mRNA element that regulates downstream encoded modification enzymes of queuosine biosynthesis. For reasons that are not presently understood, the classical pseudoknot fold of this system harbors an extra stem-loop structure within its 3'-terminal region immediately upstream of the Shine-Dalgarno sequence that contributes to formation of the ligand-bound state. By imaging ligand-dependent preQ(1) riboswitch folding from multiple structural perspectives, we reveal that the extra stem-loop strongly influences pseudoknot dynamics in a manner that decreases its propensity to spontaneously fold and increases its responsiveness to ligand binding. We conclude that the extra stem-loop sensitizes this RNA to broaden the dynamic range of the ON/OFF regulatory switch.