Lin Jong-Chin, Thirumalai D
Department of Chemistry and Biochemistry and Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742, USA.
J Am Chem Soc. 2008 Oct 29;130(43):14080-1. doi: 10.1021/ja8063638. Epub 2008 Oct 2.
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.
核糖开关的折叠由代谢物与适体结构域的结合控制，从而调节下游基因表达。适体的折叠特性强烈影响下游表达平台的构象，该平台控制转录终止或翻译起始。我们使用粗粒度自组织聚合物模型和布朗动力学模拟，通过用机械力展开和重新折叠分子，定量地表征了add核糖开关适体的能量景观。在适体的折叠过程中，无论有无腺嘌呤，都发现了多种折叠状态，这与嘌呤核糖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，其折叠过程与完整核糖开关中下游茎环结构的形成相互竞争。这些结果为RNA开关的基因调控机制提供了见解。
