美国国家癌症研究所Yun-Xing Wang课题组最新的研究，解析了RNase P RNA在溶液中的构象空间。该研究于2024年12月18日发表于国际一流学术期刊《自然》杂志上。

据了解，RNA构象多样性具有基本的生物学作用，但传统生物物理技术不可能在溶液中直接可视化其整个构象空间。

利用溶液原子力显微镜、深度神经网络和统计分析，该课题组人员发现核糖核酸酶P (RNase P) RNA采用异质构象，由构象不变的核心和高度灵活的外围结构元素组成，具有广泛的构象空间，在许多方向以非常低的净能量成本振幅可达20-60Å。增加Mg²⁺可能是通过缩小构象空间，驱动压紧和提高酶活性。

此外，空间灵活性与序列保护之间的相关和反相关分析表明，关键区域的结构和动态的功能作用都嵌入在一级序列中。这些发现揭示了在RNase P的RNA组分中，体现酶的精确性和底物混杂性的结构动力学基础。绘制RNase P RNA的构象空间，显示了研究RNA结构和动力学的一种新的通用方法。

附：英文原文

Title: The conformational space of RNase P RNA in solution

Author: Lee, Yun-Tzai, Degenhardt, Maximilia F. S., Skeparnias, Ilias, Degenhardt, Hermann F., Bhandari, Yuba R., Yu, Ping, Stagno, Jason R., Fan, Lixin, Zhang, Jinwei, Wang, Yun-Xing

Issue&Volume: 2024-12-18

Abstract: RNA conformational diversity has fundamental biological roles1,2,3,4,5, 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 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.

DOI: 10.1038/s41586-024-08336-6

Source: https://www.nature.com/articles/s41586-024-08336-6