RNA Cold Denaturation

3ROVIDED。 RNA在生物化学的许多方面发挥着核心作用。要实现这些细胞功能，至关重要的是 RNA保持其复杂的二级、三级和四级结构。此外，它正在成为 显然，RNA很容易在两个或更多稳定(或伪稳定)结构之间相互转换，作为 它们正常的生物功能。这些重排可以参与核酶活性的控制，如在 通过在5‘-中形成替代结构对接或翻译控制信使核糖核酸。 或3‘-UTRs。这个项目围绕着理解结构变化的热力学基础。 在某些RNA中观察到。我们关注的一种结构变化是冷变性过程 在那里，RNA在低温下展开。对这些过程特别重要的是热量的变化 折叠时的容量(ACP)，这是一种以前被认为微不足道但现在被证明是重要的属性 在某些情况下。锤头状核酶的冷变性是迄今为止研究得最好的，而 第一个具体目标的重点。然后将冷变性的热力学与 由高温和杂醇剂引起的变性。冷变性的一般情况是 作为特定目标2的一部分以及冷变性和核转录调节之间的关系的探讨 参与冷休克反应的过程。涉及到来自E.coil的一种称为DSRA的小型非编码RNA 在调节这一过程中，我们正在探索这种RNA的结构变化以及这些结构是如何 变化会影响它与蛋白质(Hfq)和其他RNA形成的复合体。这方面的第三个主要目标 建议在核酸折叠中观察AH和ACP的潜在性质，并了解 金属水化/脱水反应对三元系总能量的热力学贡献 RNA的结构形成。

3ROVIDED. RNA plays a central role in many aspects of biochemistry. To carry out these cellular functions, it is critical that RNAs maintain their complex secondary, tertiary and quaternary structures. Furthermore, it is becoming evident that RNAs readily interconvert between two or more stable (or pseudo-stable) structures as part of their normal biological function. These rearrangements can be involved in control of ribozyme activity as in the case of docking, or translational control of an mRNA through formation of alternative structures in the 5'- or 3'-UTRs. This project revolves around understanding the thermodynamic basis for the structural changes observed in certain RNAs. One type of structural change we focus on is the process of cold denaturation where RNAs unfold at low temperature. Of particular importance to these processes is the change in heat capacity (ACp) upon folding, a property previously believed to be negligible but now shown to be significant in certain cases. The cold denaturation of the hammerhead ribozyme is the best studied to date and the focus of the first specific aim. The thermodynamics to cold denaturation will then be compared to denaturation induced by high temperature and chaotropic agents. The generality of cold denaturation will be probed as part of specific aim 2 as well as the relationship between cold denaturation and riboregulation processes involved in the cold shock response. A small non-coding RNA from E. coil called DsrA is involved in regulating this process are we are probing the structural changes of this RNA and how these structural changes affect the complexes it makes with proteins (Hfq) and other RNAs. The 3rd major goal of this proposal is to look a the underlying nature of AH and ACp in nucleic acid folding and understand the thermodynamic contribution of metal hydration/dehydration reactions on the overall energetics of tertiary structure formation of RNAs.