文献类型：会议论文

中文题名：Characterization of Base-pairing of RNA in RNA Gels Formed by Nucleotide Repeat Expansion by Proton-detected Solid-state NMR

作者：Sha Zhao[1,2];Ziyang Wen[1];Mengbing Zou[1,2];Shenlin Wang[1,2,3,4]

机构：[1]College of Chemistry and Molecular Engineering,Peking University;[2]Beijing NMR Center,Peking University;[3]Beijing National Laboratory for Molecular Sciences;[4]State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology

会议论文集：2021年全国生物相分离和相变学术研讨会论文集

会议日期：20210408

会议地点：中国广东深圳

语种：英文

中文关键词：RNA;Phase separation;Solid-state NMR

摘要：Hexanucleotide repeat expansions of C9 orf72,（GGGGCC）n, are related to neurological diseases,including amyotrophic lateral sclerosis（ALS） and frontotemporal dementia（FTD）.Previous study showed that C9 orf72 hexanucleotide repeat undergoes a soluble to gel transition in vitro without protein partners.Formation of G-quadruplex was believed to be the main driving force of the phase transition involving the GGGGCC repeats.However,observation of the secondary structure of（GGGGCC）n in RNA gels is still lacking.Understanding the key structural components would provide valuable insights into the mechanisms of RNA phase separation and clues in drug discovery.Solid-state NMR is powerful in characterization of bio-macromolecules within the condensed-phase systems.Here,we report our recent advancements of novel 2 D proton-detected SSNMR experiments to analyze the base-pairings of RNA in solids.Applied on（GGGGCC）s repeats,our results revealed that both the G-C Watson-Crick base pairs and the G-G base pairs exist in（GGGGCC）s RNA gels in the presence of Mg.In contrast,the G-quadruplex was not observed in this state.This observation is different from the early solution NMR studies,which showed major G-quadruplex topology in Kcontaining solution.It suggests structural rearrangements of（GGGGCC） in forming RNA gels from monomers or low number of oligomers.To data,our results provide the first direct structural evidence on RNA in insoluble gel-like state,facilitating in understanding the key driving forces of RNA foci.This approach is adaptable to other phase separation systems involving RNA molecules.