Department of Pharmaceutical Sciences, University of California, Irvine. Irvine, CA 92697, USA.
Department of Developmental and Cellular Biology, University of California, Irvine. Irvine, CA 92697, USA.
Nucleic Acids Res. 2021 Nov 18;49(20):11868-11882. doi: 10.1093/nar/gkab885.
RNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptome-wide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.
RNA 分子可以折叠成复杂的结构，并与反式作用因子相互作用，从而控制其生物学功能。最近的方法主要集中在开发新的工具，以在转录组范围内测量 RNA 结构，但迄今为止，它们在研究和预测 RNA-蛋白质相互作用或 RNA 加工方面的应用受到限制。在这里，我们通过首次在转录组范围内对 RNA 溶剂可及性进行编目的方法 icLASER，扩展了这些研究。通过将溶剂可及性 (icLASER) 与 RNA 柔韧性 (icSHAPE) 数据相结合，我们可以高效地预测转录组范围内的 RNA-蛋白质相互作用，并仅通过 RNA 结构对 RNA 多聚腺苷酸化位点进行编目。这些研究展示了设计新型化学方法研究 RNA 生物学的威力。此外，我们的研究还例证了将互补方法结合起来，在细胞内测量 RNA 结构及其在预测对 RNA 结构的控制和调节至关重要的转录组范围内相互作用的实用性。我们设想可以将这些方法应用于研究不同类型的细胞或在不同条件下的细胞，使用 RNA 结构和足迹分析来描述涉及 RNA 的细胞相互作用和加工。
