MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structures, Tsinghua University, Beijing, 100084, China.
Nat Struct Mol Biol. 2019 Apr;26(4):322-330. doi: 10.1038/s41594-019-0200-7. Epub 2019 Mar 18.
RNA structure is intimately connected to each step of gene expression. Recent advances have enabled transcriptome-wide maps of RNA secondary structure, called 'RNA structuromes'. However, previous whole-cell analyses lacked the resolution to unravel the landscape and also the regulatory mechanisms of RNA structural changes across subcellular compartments. Here we reveal the RNA structuromes in three compartments, chromatin, nucleoplasm and cytoplasm, in human and mouse cells. The cytotopic structuromes substantially expand RNA structural information and enable detailed investigation of the central role of RNA structure in linking transcription, translation and RNA decay. We develop a resource with which to visualize the interplay of RNA-protein interactions, RNA modifications and RNA structure and predict both direct and indirect reader proteins of RNA modifications. We also validate a novel role for the RNA-binding protein LIN28A as an N-methyladenosine modification 'anti-reader'. Our results highlight the dynamic nature of RNA structures and its functional importance in gene regulation.
RNA 结构与基因表达的每一个步骤都密切相关。最近的进展使得能够绘制 RNA 二级结构的转录组范围图谱,称为“RNA 结构组学”。然而,以前的全细胞分析缺乏分辨率来揭示 RNA 结构在亚细胞区室之间变化的全景和调控机制。在这里,我们在人类和小鼠细胞中揭示了染色质、核质和细胞质这三个区室的 RNA 结构组学。细胞定位结构组学大大扩展了 RNA 结构信息,并能够详细研究 RNA 结构在连接转录、翻译和 RNA 降解中的核心作用。我们开发了一个资源,用于可视化 RNA-蛋白质相互作用、RNA 修饰和 RNA 结构的相互作用,并预测 RNA 修饰的直接和间接阅读器蛋白。我们还验证了 RNA 结合蛋白 LIN28A 作为 N6-甲基腺苷修饰“反阅读器”的新作用。我们的结果强调了 RNA 结构的动态性质及其在基因调控中的功能重要性。