Visualizing RNA Conformational Changes via Pattern Recognition of RNA by Small Molecules
Visualizing RNA Conformational Changes via Pattern Recognition of RNA by Small Molecules
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DOI：
10.1021/jacs.8b09665
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发表时间：
2019-04-10
影响因子：
15
通讯作者：
Hargrove, Amanda E.
中科院分区：
文献类型：
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作者：
Eubanks, Christopher S.;Zhao, Bo;Hargrove, Amanda E.
RNA的构象变化在许多生物系统的调节中起着至关重要的作用，但这些变化可能具有挑战性。先前，我们证明了小分子RNA模式识别（PRRSM）可以无偏地利用氨基糖苷类受体库聚类定义的RNA二级结构基序。在这项工作中，我们展示了这种方法的力量，可视化的变化折叠在二级结构水平内两个不同的核糖开关结构。在每个核糖开关上的三个独立位置标记后，PRRSM准确地将所有载脂蛋白和配体结合的核糖开关结构分类，包括结构基序大小的变化，并揭示了防止折叠和/或导致混合状态的修饰位点。这些数据强调了PRRSM测定用于快速评估RNA结构变化和用于获得对RNA折叠至关重要的核苷酸位置的即时洞察的实用性和稳健性。
Conformational changes in RNA play vital roles in the regulation of many biological systems, yet these changes can be challenging to visualize. Previously, we demonstrated that Pattern Recognition of RNA by Small Molecules (PRRSM) can unbiasedly cluster defined RNA secondary structure motifs utilizing an aminoglycoside receptor library. In this work, we demonstrate the power of this method to visualize changes in folding at the secondary structure level within two distinct riboswitch structures. After labeling at three independent positions on each riboswitch, PRRSM accurately classified all apo and ligand-bound riboswitch structures, including changes in the size of a structural motif, and revealed modification sites that prevented folding and/or led to a mixture of states. These data underscore the utility and robustness of the PRRSM assay for rapid assessment of RNA structural changes and for gaining ready insight into nucleotide positions critical to RNA folding.