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Structural and dynamic properties of the YTH domain in complex with N^(6)-methyladenosine RNA studied by accelerated molecular dynamics simulations

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Quantitative biology 2023年第1期11卷 72-81页

作者： Mingwei Li Guanglin Chen Zhiyong Zhang MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics National Science Center for Physical Sciences at MicroscaleDivision of Life Sciences and Medicineand Biomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China Department of Physics University of Science and Technology of ChinaHefei 230026China

Background:N^(6)-methyladenosine(m^(6)A)modifications of mRNA and long non-coding RNA(lncRNAs)are known to play a significant role in regulation of gene expression and organismal *** writer and eraser proteins of this dynamic modification,the YT521-B homology(YTH)domain can recognize the modification involved in numerous cellular *** function of proteins containing YTH domain and its binding mode with N^(6)-methyladenosine RNA has attracted considerable ***,the structural and dynamic characteristics of the YTH domain in complex with m^(6)A RNA is still ***:This work presents results of accelerated molecular dynamics(aMD)simulations at the timescale of *** component analysis(PCA),molecular mechanics generalized Born surface area(MM/GBSA)calculations,contact analysis and contact-based principal component analysis(conPCA)provide new insights into structure and dynamics of the YTH-RNA ***:The aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH-A3 RNA than that in the YTH-m^(6)A3 *** aMD trajectories of the apo YTH,there is a significant close-open transition of the recognition loop,that is to say,the apo YTH can take both the closed and open *** have found that the YTH domain binds more favorably to the methylated RNA than the nonmethylated *** per-residue free energy decomposition and conPCA suggest that hydrophobic residues including W380,L383-V385,W431-P434,M437,and M441-L442,may play important roles in favorable binding of the m^(6)A RNA to the YTH domain,which is also supported by aMD simulations of a double mutated system(L383A/M437A).Conclusion:The results are in good agreement with higher structural stability of the YTH-m^(6)A RNA than that of the YTH-A3 *** addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH *** simulations support a‘conformational

关键词： RNA methylation YTH-m^(6)A3 RNA principal component analysis(PCA) binding free energy contactbased PCA

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IL-18 maintains the homeostasis of mucosal immune system via inflammasome-independent but microbiota-dependent manner

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Science Bulletin 2021年第20期66卷 2115-2123,M0004页

作者： Xuesen Zheng Lei Liu Guangxun Meng Shu Zhu Rongbin Zhou Wei Jiang Hefei National Laboratory for physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China The center for Microbes Development and HealthKey Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China CAS center for Excellence in Cell and Molecular biology University of Science and Technology of ChinaHefei 230027China

Inflammasomes and their product interleukin 18(IL-18)play important roles in gut microbiota monitoring and homeostasis,and their loss of function could lead to microbiota dysbiosis and accelerate disease ***,the impacts of the resulting microbiota dysbiosis on the mucosal immune system are largely ***,we show that dysbiotic microbiota from Il18^(-/-)mice induced immune cell loss in the small intestine(SI)in an inflammasome-independent *** experiments revealed that the immunotoxic phenotype of these microbiota was transferable to wild type(WT)mice and induced immune cell death through the receptor-interacting protein kinase 3(RIP3)-mixed lineage kinase domain like pseudokinase(MLKL)*** of microbiota composition identified two types of bacteria at the genus level,Ureaplasma and Parasutterella,that accumulated in Il18^(-/-)mice and negatively mediated changes in immune cells in the ***,dysbiosis in Il18^(-/-)mice also contributed to increased susceptibility to Listeria ***,our results demonstrate that IL-18 is essential to microbiota homeostasis and that dysbiotic microbiota could significantly shape the landscape of the immune system.

关键词： Dysbiosis Immune system IL-18 Inflammasome

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Identification of mecciRNAs and their roles in the mitochondrial entry of proteins

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Science China(Life Sciences) 2020年第10期63卷 1429-1449页

作者： Xu Liu Xiaolin Wang Jingxin Li Shanshan Hu Yuqi Deng Hao Yin Xichen Bao Qiangfeng Cliff Zhang Geng Wang Baolong Wang Qinghua Shi Ge Shan Deparment of Clinical Laboratory The Firs Ajiaued Hospital of USICHefei National Laborarory for Physical Sciences an Microscalethe CAS Key Laboratory of Inmate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Neurosurgery The First Afiliated Hospial of University of Science and Technology of China Hefei 230001China Key Laboratory of Regeneralive biology of the Chinese Academy of Sciences Joint School of Life SciencesGuangzhou Medical Untiversily and Guangzhou Institutes of Biomedicine and HealhChinese Academy of SciencesGuangzhou 510530China MOE Key Laboratory of Bioinformatics School of Life SciencesTsinghua UniversiyBeiing 100084.China CAS center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Mammalian mitochondria have small genomes encoding very limited numbers of *** one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the ***,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial *** provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported *** components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein *** expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein *** and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.

关键词： mitochondria circRNA mecciRNA mitochondrial protein import

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Cytokine storm and translating IL-6 biology into effective treatments for CoVID-19

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Frontiers of Medicine 2023年第6期17卷 1080-1095页

作者： Tiantian Li Dongsheng Wang Haiming Wei Xiaoling Xu Department of Geriatric Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Respiratory and Critical Care Medicine The First Afiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Science and Medical CenterUniversity of Science and Technology of ChinaHefei 230001China Hefei National Laboratory for physical Sciences at Microscale University of Science and Technology of ChinaHefei 230001China

As of May 3,2023,the Coronavirus disease 2019(COVID-19)pandemic has resulted in more than 760 million confirmed cases and over 6.9 million *** patients have developed pneumonia,which can deteriorate into acute respiratory distress *** primary etiology may be attributed to cytokine storm,which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune *** that high levels of interleukin-6(IL-6)have been detected in several highly pathogenic coronavirus-infected diseases,such as severe acute respiratory syndrome in 2002,the Middle East respiratory syndrome in 2012,and COVID-19,the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory ***,we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2 COVID-19 cytokine storm interleukin-6 tocilizumab

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Inhibition of miR397 by STTM technology to increase sweetpotato resistance to SPVD

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Journal of Integrative Agriculture 2022年第10期21卷 2865-2875页

作者： LI Chen LIU Xuan-xuan ABOUELNASR Hesham MOHAMED HAMED Arisha KOU Meng TANG Wei YAN Hui WANG Xin WANG Xiao-xiao ZHANG Yun-gang LIU Ya-ju GAO Run-fei MA Meng LI Qiang Xuzhou Institute of Agricultural Sciences in Jiangsu Xuhuai District/Sweetpotato Research Institute Chinese Academy of Agricultural Sciences/Key Laboratory of Biology and Genetic Breeding of SweetpotatoMinistry of Agriculture and Rural AffairsXuzhou 221131P.R.China School of Life Science Jiangsu Normal UniversityXuzhou 221116P.R.China Plant Pathology Department Agriculture and Biology Research DivisionNational Research CenterGiza 12622Egypt Department of Horticulture Faculty of AgricultureZagazig UniversityZagazig 44511Egypt

As a critical food crop,sweetpotato(Ipomoea batatas(L.)Lam.)is widely planted all over the world,but it is deeply affected by Sweetpotato Virus Disease(SPVD).The present study utilized short tandem target mimic(STTM)technology to effectively up-regulate the expression of laccase(Ib LACs)by successfully inhibiting the expression of mi *** upstream genes in the lignin synthesis pathway were widely up-regulated by feedback regulation,including phenylalanine ammonialyase(PAL),4-coumarate-Co Aligase(4 CL),hydroxycinnamoyl Co A:shikimatetransferase(HTC),caffeicacid O-methyltransferase(COMT),and cinnamyl alcohol dehydrogenase(CAD).Meanwhile,the activities of PAL and LAC increased significantly,finally leading to increased lignin *** deposition in the cell wall increased the physical defence ability of transgenic sweetpotato plants,reduced the accumulation of SPVD transmitted by Bemisia tabaci(Gennadius),and promoted healthy sweetpotato *** results provide new insights for disease resistance breeding and green production of sweetpotato.

关键词： sweetpotato miR397 STTM SPVD lignin content

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Inactivation of OslRX10 Leads to Decreased Xylan Content in Rice Culm Cell Walls and Improved Biomass Saccharification

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Molecular Plant 2013年第2期6卷 570-573页

作者： Xuewei Chen Miguel E. Vega-Sanchez Yves Verhertbruggenb Dawn Chiniquy Patrick E. Canlas Alexandra Fagerstrom Lina Prak Ulla Christensen Ai Oikawa Mawsheng Chern Shimin Zuo Fan Lin Manfred Auer William G.T. Willats Laura Bartley Jesper Harholt Henrik V. Scheller Pamela C. Ronald Department of Plant Pathology and The Genome center University of California Davis CA 95616 USA Joint BioEnergy Institute Emeryville CA 94608 USA Rice Research Institute Sichuan Agricultural University at Wenjiang Wenjiang Chengdu 611130 China physical Biosciences division Lawrence Berkeley National Laboratory Berkeley CA 94720 USA Department of Plant and Environmental Sciences Faculty of Science University of Copenhagen DK-1871 Frederiksberg Denmark Department of Botany and Microbiology University of Oklahoma Norman OK 73019 USA Department of Plant and Microbial biology University of California Berkeley CA 94720 USA

Dear Editor, Xylan polysaccharides constitute the major non-cellulosic components in secondary cell walls of dicots and in both primary and secondary cell walls of grasses （Scheller and Ulvskov, 2010）. Xylan is composed of a linear backbone of 13（1-4）-linked xylose （Xyl）. In grasses, the xylan backbone is substituted with 03-1inked and 02-1inked arabinose residues and, to a lesser extent, a（1-3）-Iinked glucuronic acid residues.

关键词： ARABIDOPSIS

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APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation

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Protein & Cell 2023年第12期14卷 908-913页

作者： Hongkai Zhao Kuan Yang Yiyuan Zhang Hongyu Li Qianzhao ji Zeming Wu Shuai Ma Si Wang Moshi Song Guang-Hui Liu Qiang Liu Weiqi Zhang Jing Qu division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China State Key Laboratory of Stem Cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Universityof Chinese Academy of Sciences Beijing100049China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical University.Beijing100053China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Aging Biomarker Consortium Beijing 100101China 12division of Life Sciences and Medicine Institute on Aging and Brain DisordersThe First Affiliated Hospital of USTCHefei National Laboratory for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230026China Neurodegenerative Disease Research center University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory of Brain Function and Disease University of Science and Technology of ChinaHefei 230026China center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650201China

Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death ***,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.

关键词： cardiovascular metabolism

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Physiological and pathological insights into exosomes in the brain

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Zoological Research 2020年第4期41卷 365-372页

作者： Xiao-Hui Li Juan Zhang Ding-Feng Li Wei Wu Zhong-Wen Xie Qiang Liu Institute on Aging and Brain Disorders The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineHefei National Laboratory for Physical Sciences at the MicroscaleSchool of Life SciencesUniversity of Science and Technology of ChinaHefeiAnhui230001China State Key Laboratory of Tea Plant biology and Utilization Anhui Agricultural UniversityHefeiAnhui 230036China Neurodegenerative Disease Research center University of Science and Technology of ChinaHefeiAnhui 230026China Organ Transplantation center The First Affiliated Hospital of University of Science and Technology of ChinaHefeiAnhui 230026China CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefeiAnhui 230029China CAS Key Laboratory of Brain Function and Disease University of Science and Technology of ChinaHefeiAnhui 230026China

Exosomes are small vesicles secreted by all cell types in the brain and play a role in cell-cell communication through the transfer of cargo or *** in the brain have considerable impact on neuronal development,activation,and *** addition,exosomes are reported to be involved in the onset and propagation of various neurodegenerative *** this review,we discuss the content of exosomes derived from major cell types in the brain,and their function under physiological and pathological conditions.

关键词： pathological Exosomes insight

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Action mode of NPA:direct inhibition on PIN auxin transporters

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Molecular Plant 2021年第2期14卷 199-199页

作者： Shutang Tan School of Life Sciences Division of Life Sciences and Medicineand Division of Molecular&Cell BiophysicsHefei National Science Center for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230027China

Chemical tools play essential roles in dissecting the molecular mechanisms underlying biological processes in living *** the history of plant biology,N-1-naphthylphthalamic acid(NPA)has long been used as an auxin export inhibitor,and multiple in vivo targets have been proposed,such as ABC transporters,TWISTED DWARF1,and BIG/-rlR3(reviewed in Teale and Palme,2018).These proteins exhibit pleiotropic functions,which were proposed to indirectly mediate the NPA effect through the activity or trafficking of PIN-FORMED(PIN)auxin ***,the debate on the pure target of N PA often makes a clear interpretation of such experimental data elusive.

关键词： Action auxin mode

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Osteomodulin downregulation is associated with osteoarthritis development

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Bone Research 2023年第4期11卷 721-736页

作者： Jérémie Zappia Qiao Tong Renée Van der Cruyssen Frederique MFCornelis Cécile Lambert Tiago Pinto Coelho Juliane Grisart Erika Kague Rik JLories Marc Muller Dirk Elewaut Chrissy LHammond Christelle Sanchez Yves Henrotin MusculoSKeletal Innovative Research Lab Center for Interdisciplinary Research on MedicinesUniversitéde LiègeLiègeBelgium School of Physiology Pharmacologyand NeuroscienceUniversity of BristolBristolUK Department of Biomedical Molecular biology Ghent UniversityGhentBelgium Laboratory for Molecular Immunology and Inflammation Department of RheumatologyGhent University HospitalGhentBelgium Laboratory of Tissue Homeostasis and Disease Skeletal Biology and Engineering Research CenterDepartment of Development and RegenerationKU LeuvenLeuvenBelgium Cardiovascular Sciences Groupe Interdisciplinaire de Génoprotéomique AppliquéeUniversitéde LiègeLiègeBelgium division of Nephrology CHU of LiègeUniversitéde LiègeLiègeBelgium Artialis SA Tour GIGACHU Sart-TilmanLiègeBelgium division of Rheumatology University Hospitals LeuvenLeuvenBelgium Laboratoire d’Organogenèse et Régénération Groupe Interdisciplinaire de Génoprotéomique AppliquéeUniversitéde LiègeLiègeBelgium physical Therapy and Rehabilitation Department Princess Paola HospitalVivaliaMarche-en-FamenneBelgium

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis(OA), and osteomodulin(OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.

关键词： metabolism conclusion homeostasis

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