文献类型：期刊文献

中文题名：Phase separation of hnRNPA1 and TERRA regulates telomeric stability

作者：Ziyan Xu[1,2,3];Yongrui Liu[1,2,3];Fudong Li[1,2,3];Yi Yang[4];Hong Zhang[5,6];Feilong Meng[7];Xing Liu[1,2,3];Xin Xie[4];Xianjun Chen[4];Yunyu Shi[1,2,3];Liang Zhang[1,2,3]

机构：[1]Center for Advanced Interdisciplinary Science and Biomedicine of IHM,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China;[2]Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China;[3]Hefei National Research Center for Cross-disciplinary Science,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China;[4]Optogenetics and Synthetic Biology Interdisciplinary Research Center,State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;[5]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Be?ing 100101,China;[6]College of Life Sciences,University of Chinese Academy of Sciences,Be?ing 100049,China;[7]State Key Laboratory of Molecular Biology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China

年份：2024

卷号：16

期号：9

起止页码：25

中文期刊名：Journal of Molecular Cell Biology

外文期刊名：分子细胞生物学报(英文版)

收录：CSCD:【CSCD2023_2024】；

基金：supported by the National Natural Science Foundation of China(32090040,32293213,and 92149302);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37010105 and XDB39010300);the Fundamental Research Funds for the Central Universities(WK9100000067);the Ministry of Science and Technology of China(2019YFA0508403 and 2022YFA1303100).

语种：英文

中文关键词：phase separation;crystal structure;telomeric stability;protein-RNA complex;hnRNPA1;TERRA

摘要：Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin.As a result of the DNA replication ending issue,telomeric DNA shortens during each cell cycle.The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA.The stability of telomeres is critical for cellular function and related to the progression of many human diseases.Telomeric repeat-containing RNA(TERRA)is a noncoding RNA transcribed from telomeric DNA regions.TERRA plays an essential role in regulating and maintaining the stability of telomeres.Heterogeneous nuclear ribonucleoproteins(hnRNPs)are RNA-binding proteins associated with complex and diverse biological processes.hnRNPA1 can recognize both TERRA and telomeric DNA.Previous research reported that hnRNPA1,TERRA,and POT1,a component of the shelterin complex,work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication,promoting telomere capping to preserve genomic integrity.However,the detailed molecular mechanism has remained unclear for>20 years.Here,our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA.Furthermore,we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1,while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo.Taken together,these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.