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The development and applications of integrative methods for RNA structural biology

Abstract:RNAs are essential biomolecules that play diverse roles in many cellular processes and have been closely linked to human health and diseases. A detailed study of RNA 3D structure, dynamics and interactions are crucial for understanding the mechanisms of RNA functions and development of new therapeutics, which however remain challenging using conventional structural techniques including X-ray crystallography, NMR and cryo-EM. There is a growing trend in the field to comprehensively analyze RNA structure and dynamics by combined use of multiple complementary experimental and computational techniques, in other words, integrative methods. Recently, we have developed a novel method for posttranscriptional site-specific labeling of very large RNAs with gold nanoparticles, spin labels or fluorescent tags using the TPT3-NaM unnatural base pair system, which opens the possibility for applications of the molecular ruler techniques including X-ray scattering interferometry (XSI), Pulsed electron-electron double resonance (PELDOR) spectroscopy and single molecule fluorescence resonance energy transfer (smFRET) in investigating the structure and dynamics of large RNAs and RNA-protein complexes. Empowered by the RNA labeling method and molecular ruler techniques, we develop integrative methods for 3D structure determination of large RNA and RNA-protein complexes, which have been demonstrated in the structural, dynamic and interaction studies of flaviviral RNAs.


报告人简介:方显杨,清华大学生命学院副教授、博士生导师。2002年毕业于武汉大学化学学院,2008年于中科院生物物理所获博士学位,其后在美国国立卫生研究院国立癌症研究所从事博士后研究。2015年至今任清华大学生命学院教研系列助理教授、副教授; 2023年将任中科院生物物理所研究员、博士生导师。其课题组主要开展RNA整合结构生物学的研究,曾获海外高层次人才项目、基金委重点支持项目、科技部重点研发计划项目等资助,研究成果在Cell, PNAS, Nat.Commun., EMBO J, Chem. Sci., NAR, EMBO Reports等期刊发表。

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