Using simulations and kinetic network models to reveal the dynamics and functions of riboswitches.
Using simulations and kinetic network models to reveal the dynamics and functions of riboswitches.
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DOI：
10.1016/bs.mie.2014.10.062
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发表时间：
2015
影响因子：
--
通讯作者：
Thirumalai D
中科院分区：
文献类型：
--
作者：
Lin JC;Yoon J;Hyeon C;Thirumalai D
核糖开关是在非翻译区发现的 RNA 元件，通过与目标代谢物以精确的特异性结合来调节基因表达。代谢物与保守适体结构域的结合以变构方式改变下游表达平台的构象。基因表达的命运由下游RNA序列的变化决定。由于核糖开关依赖于代谢物的共转录折叠和解折叠动力学是基因表达的关键决定因素，因此研究存在和不存在代谢物时核糖开关的热力学和动力学非常重要。单分子力实验从机械响应中解读核糖开关的自由能景观，理论和计算研究最近揭示了不同类别核糖开关折叠动力学的独特机制。在这里，我们首先讨论核糖开关周围的水动力学，强调水动力学可以增强核酸结构的波动。为了超越天然状态波动，我们使用自组织聚合物模型来预测机械力下添加腺嘌呤核糖开关的动力学。除了定量预测 add-核糖开关的折叠景观外，我们的模拟还解释了 pbuE 腺嘌呤核糖开关和 add 腺嘌呤核糖开关之间的动力学差异。为了探究体内的功能，我们利用折叠景观提出了系统级动力学网络模型，以定量预测受动力学控制的核糖开关的基因表达是如何调节的。
Riboswitches, RNA elements found in the untranslated region, regulate gene expression by binding to target metaboloites with exquisite specificity. Binding of metabolites to the conserved aptamer domain allosterically alters the conformation in the downstream expression platform. The fate of gene expression is determined by the changes in the downstream RNA sequence. As the metabolite-dependent cotranscriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate both the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolite. Single molecule force experiments that decipher the free energy landscape of riboswitches from their mechanical responses, theoretical and computational studies have recently shed light on the distinct mechanism of folding dynamics in different classes of riboswitches. Here, we first discuss the dynamics of water around riboswitch, highlighting that water dynamics can enhance the fluctuation of nucleic acid structure. To go beyond native state fluctuations, we used the Self-Organized Polymer model to predict the dynamics of add adenine riboswitch under mechanical forces. In addition to quantitatively predicting the folding landscape of add-riboswitch, our simulations also explain the difference in the dynamics between pbuE adenine- and add adenine-riboswitches. In order to probe the function in vivo, we use the folding landscape to propose a system level kinetic network model to quantitatively predict how gene expression is regulated for riboswitches that are under kinetic control.
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DOI：
10.1073/pnas.1115045109
发表时间：
2012-01-31
影响因子：
11.1
作者：
Anthony, Peter C.;Perez, Christian F.;Block, Steven M.
通讯作者：
Block, Steven M.
DOI：
10.1126/science.1225722
发表时间：
2012-10-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Frieda KL;Block SM
通讯作者：
Block SM
影响因子：
5.7
作者：
Hyeon, Changbong;Dima, Ruxandra I.;Thirumalai, D.
通讯作者：
Thirumalai, D.
DOI：
10.1261/rna.037549.112
发表时间：
2013-07
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Allnér O;Nilsson L;Villa A
通讯作者：
Villa A
影响因子：
15
作者：
Lin, Jong-Chin;Thirumalai, D.
通讯作者：
Thirumalai, D.