RNA conformational diversity has fundamental biological roles^1,2,3,4,5, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20–60 Å in a multitude of directions, with very low net energy cost. Increasing Mg²⁺ drives compaction and enhances enzymatic activity, probably by narrowing the conformational space. Moreover, analyses of the correlations and anticorrelations between spatial flexibility and sequence conservation suggest that the functional roles of both the structure and dynamics of key regions are embedded in the primary sequence. These findings reveal the structure–dynamics basis for the embodiment of both enzymatic precision and substrate promiscuity in the RNA component of the RNase P. Mapping the conformational space of the RNase P RNA demonstrates a new general approach to studying RNA structure and dynamics.

RNA 构象多样性具有基本的生物学作用^{1,2,3,4,5，但}使用传统的生物物理技术无法直接可视化其在溶液中的完整构象空间。使用溶液原子力显微镜、深度神经网络和统计分析，我们表明核糖核酸酶 P （RNase P） RNA 采用异质构象，该构象由构象不变的核心和高度灵活的外周结构元件组成，这些构象空间采样宽阔，在多个方向上振幅高达 20-60 Å，净能量成本非常低。增加 Mg²⁺ 驱动压实并增强酶活性，可能是通过缩小构象空间。此外，对空间灵活性和序列守恒性之间相关性和反相关性的分析表明，关键区域的结构和动力学的功能作用都嵌入在初级序列中。这些发现揭示了 RNase P 的 RNA 组分中酶精度和底物混杂的结构-动力学基础。绘制 RNase P RNA 的构象空间展示了一种研究 RNA 结构和动力学的新通用方法。