Relative Stability of Helices Determines the Folding Landscape of Adenine Riboswitch Aptamers
Relative Stability of Helices Determines the Folding Landscape of Adenine Riboswitch Aptamers
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DOI：
10.1021/ja8063638
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发表时间：
2008-10-29
影响因子：
15
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Lin, Jong-Chin;Thirumalai, D.
核糖开关的折叠是通过代谢产物与适体结构域的结合来控制的，它调节下游基因的表达。适体的折叠特性强烈影响下游表达平台的构象，从而控制转录终止或翻译起始。我们利用粗粒自组织聚合物模型和布朗动力学模拟，通过机械力展开和再折叠分子，定量表征了添加核糖开关适配体的能量格局。在核酸适配体的折叠过程中发现了多种折叠状态，包括有和没有腺嘌呤的折叠状态，这与嘌呤核开关的单分子研究一致。腺嘌呤结合稳定了折叠结构，并显著降低了适体的展开速率，适体的折叠与完整核糖开关中下游茎环结构的形成是竞争的。这些结果为RNA开关调控基因的机制提供了新的见解。
Riboswitches, whose folding is controlled by binding of metabolites to the aptamer domain, regulate downstream gene expression. Folding properties of the aptamer strongly influence the conformation of the downstream expression platform, which controls transcription termination or translation initiation. We have characterized the energy landscape of the add riboswitch aptamer quantitatively by unfolding and refolding the molecule with mechanical force using the coarse-grained self-organized polymer model and Brownian dynamics simulation. Multiple folding states have been found during the folding process of the aptamer, both with and without adenine, consistent with single molecule studies of purine riboswitches. Adenine binding stabilizes the folded structure and significantly decreases the unfolding rate of the aptamer, the folding of which is in competition with the formation of the downstream stem-loop structure in the complete riboswitch. These results provide insights into the mechanism of gene regulation by the RNA switches.