Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States.
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States.
Methods Enzymol. 2022;673:53-76. doi: 10.1016/bs.mie.2022.04.004. Epub 2022 May 14.
RNA helicase proteins perform coupled reactions in which cycles of ATP binding and hydrolysis are used to drive local unwinding of double-stranded RNA (dsRNA). For some helicases in the ubiquitous DEAD-box family, these local unwinding events are integral to folding transitions in structured RNAs, and thus these helicases function as RNA chaperones. An important measure of the efficiency of the helicase-catalyzed reaction is the ATP utilization value, which represents the average number of ATP molecules hydrolyzed during RNA unwinding or a chaperone-assisted RNA structural rearrangement. Here we outline procedures that can be used to measure the ATP utilization value in RNA unwinding or folding transitions. As an example of an RNA folding transition, we focus on the refolding of the Tetrahymena thermophila group I intron ribozyme from a long-lived misfolded structure to its native structure, and we outline strategies for adapting this assay to other RNA folding transitions. For a simple dsRNA unwinding event, the ATP utilization value provides a measure of the coupling between the ATPase and RNA unwinding activities, and for a complex RNA structural transition it can give insight into the scope of the rearrangement and the efficiency with which the helicase uses the energy from ATPase cycles to promote the rearrangement.
RNA 解旋酶蛋白进行偶联反应,其中 ATP 的结合和水解循环被用来驱动双链 RNA(dsRNA)的局部解旋。对于普遍存在的 DEAD 盒家族中的一些解旋酶,这些局部解旋事件是结构 RNA 折叠转变的组成部分,因此这些解旋酶作为 RNA 分子伴侣发挥作用。解旋酶催化反应效率的一个重要衡量标准是 ATP 利用率,它代表在 RNA 解旋或分子伴侣辅助的 RNA 结构重排过程中水解的平均 ATP 分子数。在这里,我们概述了可用于测量 RNA 解旋或折叠转变中 ATP 利用率的程序。作为 RNA 折叠转变的一个例子,我们专注于嗜热四膜虫组 I 内含子核酶从长寿命错误折叠结构到其天然结构的重折叠,并概述了将该测定法适应其他 RNA 折叠转变的策略。对于简单的 dsRNA 解旋事件,ATP 利用率提供了 ATP 酶和 RNA 解旋活性之间偶联的衡量标准,对于复杂的 RNA 结构转变,它可以深入了解重排的范围以及解旋酶利用 ATP 酶循环能量促进重排的效率。