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| 1 | Enzymatic activity and chromatographic characteristics of the cell membrane immobilized on silica surface显示文摘A new cell membrane preparation, silica carrier cell membrane (CCM), has been presented, in which cell membrane was immobilized on silica which acted as carrier by the adsorption. The surface characteristics of the silica CCM have been tested by a scanning electron microscope and surface energy spectrometer. Comparison has been made of the changeable rule of enzymatic activity of rabbit red cell membrane in three states: the silica CCM, the suspension and the precipitation cell membranes, with temperature and time. The result showed that the silica CCM still keeps the same enzymatic activity as the other two states of cell membranes. The interactions between calcium antagonists and rabbit red and cardiac muscle cell membranes, and the stereoscopic interactions between dihydropridines and rabbit cerebellar cell membrane have been investigated by the chromatographic system of the silica CCM as a stationary phase. From the foregoing results, the chromatographic parameters obtained from the system would | Langchong He Guangde Yang Xindu Geng | 1999 | Chinese Science Bulletin1999，44，9： | 58 |
| 2 | Boceprevir,GC-376,and calpain inhibitors Ⅱ,Ⅻ inhibit SARS-CoV-2 viral replication by targeting the viral main protease显示文摘A new coronavirus SARS-CoV-2,also called novel coronavirus 2019(2019-nCoV),started to circulate among humans around December 2019,and it is now widespread as a global pandemic.The disease caused by SARS-CoV-2 virus is called COVID-19,which is highly contagious and has an overall mortality rate of 6.35%as of May 26,2020.There is no vaccine or antiviral available for SARS-CoV-2.In this study,we report our discovery of inhibitors targeting the SARS-CoV-2 main protease(Mpro).Using the FRET-based enzymatic assay,several inhibitors including boceprevir,GC-376,and calpain inhibitorsⅡ,andⅫwere identified to have potent activity with single-digit to submicromolar ICs0 values in the enzymatic assay.The mechanism of action of the hits was further characterized using enzyme kinetic studies,thermal shift binding assays,and native mass spectrometry.Significantly,four compounds(boceprevir,GC-376,calpain inhibitorsⅡandⅫ)inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37μM.Notably,boceprevir,calpain inhibitorsⅡandⅫrepresent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors.A complex crystal structure of SARS-CoV-2 Mpro with GC-376,determined at 2.15(A)resolution with three protomers per asymmetric unit,revealed two unique binding configurations,shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro.Overall,the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. | Chunlong Ma Michael Dominic Sacco Brett Hurst Julia Alma Townsend Yanmei Hu Tommy Szeto Xiujun Zhang Bart Tarbet Michael Thomas Marty Yu Chen Jun Wang | 2020 | Cell Research2020，30，8： | 13 |
| 3 | Genomic and enzymatic evidence for acetogenesis among multiple lineages of the archaeal phylum Bathyarchaeota widespread in marine sediments显示文摘With the support by the National Natural Science Foundation of China,and China Ocean Mineral Resources R&D Association,the research team led by Prof.Wang Fengping(王风平)from Shanghai JiaoTong University,in cooperation with Prof.Li Meng from ShenZhen University,and Prof.Stefan M.Sievert from Woods Hole Oceanographic Institution,revealed the metabolic function of largely unknown sedi- | | 2016 | Science Foundation in China2016，24，3： | 11 |
| 4 | Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema显示文摘The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme(APE)in the management of diabetic retinopathy and diabetic macular edema(DME).Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included.All cases were treated with an initial intravitreal injection of APE and reevaluated one month later,measuring changes in best-corrected visual acuity(BCVA),macular thickness and the status of the posterior hyaloid.A second APE injection was performed in cases with no evident posterior vitreous detachment(PVD)after the initial treatment.Sixty-three eyes were included in the present review.A complete PVD appeared in 38%of cases(24 eyes)after one injection of plasmin and the total increased to 51%(32 eyes)after the second injection,separated at least by one month.The central macular thickness improved in all cases(100%)and BCVA in89%.Finally,in 50%of eyes with proliferative diabetic retinopathy,a high reduction of new vessels regression was observed.Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema. | Manuel Diaz-Llopis Patricia Udaondo Jose Maria Millán J Fernando Arevalo | 2013 | World Journal of Diabetes2013，4，6： | 6 |
| 5 | Diabetic macular edema:Current management 2013显示文摘Diabetic retinopathy(DR)is the leading cause of vision loss of working-age adults,and diabetic macular edema(DME)is the most frequent cause of vision loss related to diabetes.The Wisconsin Epidemiologic Study of Diabetic Retinopathy found the 14-year incidence of DME in type 1 diabetics to be 26%.Similarly the Diabetes Control and Complications Trial reported that 27% of type 1 diabetic patients develop DME within9 years of onset.The most common type of diabetes,type 2,is strongly associated with obesity and a sedentary lifestyle.An even higher incidence of macular edema has been reported in older patients with type 2diabetes.Within the last 5 years,the use of intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor(VEGF)agents have come into clinical practice for the management of DME and several recent randomized clinical trials have shown improved effectiveness of ranibizumab compared to focal/grid laser.In this theme issue,we discuss the classification of DR and the treatment options currently available for the treatment of DME including corticosteroids,anti-VEGF agents,combined therapy,enzymatic vitrectomy(vitreolysis),and new therapies. | J Fernando Arevalo | 2013 | World Journal of Diabetes2013，4，6： | 5 |
| 6 | Intensifying Electron Utilization by Surface-Anchored Rh Complex for Enhanced Nicotinamide Cofactor Regeneration and Photoenzymatic CO_(2)Reduction显示文摘Solar-driven photocatalytic regeneration of cofactors,including reduced nicotinamide adenine dinucleotide(NADH),reduced nicotinamide adenine dinucleotide phosphate(NADPH),and reduced flavin adenine dinucleotide(FADH_(2)),could ensure the sustainable energy supply of enzymatic reactions catalyzed by oxidoreductases for the efficient synthesis of chemicals.However,the elevation of cofactor regeneration efficiency is severely hindered by the inefficient utilization of electrons transferred on the surface of photocatalysts.Inspired by the phenomenon of ferredoxin-NADP+reductase(FNR)anchoring on thylakoid membrane,herein,a homogeneous catalyst of rhodium(Rh)complex,[Cp_(∗)Rh(bpy)H_(2)O]^(2+),was anchored on polymeric carbon nitride(PCN)mediated by a tannic acid/polyethyleneimine(TA/PEI)adhesive layer,acquiring PCN@TA/PEI-Rh core@shell photocatalyst.Illuminated by visible light,electrons were excited from the PCN core,then transferred through the TA/PEI shell,and finally captured by the surface-anchored Rh for instant utilization during the regeneration of NADH.The TA/PEI-Rh shell could facilitate the electron transfer from the PCN core and,more importantly,achieved~1.3-fold elevation of electron utilization efficiency compared with PCN.Accordingly,the PCN@TA/PEI-Rh afforded the NADH regeneration efficiency of 37.8%after 20 min reaction under LED light(405 nm)illumination,over 1.5 times higher than PCN with free Rh.Coupling of the NADH regeneration system with formate dehydrogenase achieved continuous production of formate from carbon dioxide(CO_(2)).Our study may provide a generic and effective strategy to elevate the catalytic efficiency of a photocatalyst through intensifying the electron utilization. | Yuqing Cheng Jiafu Shi Yizhou Wu Xueying Wang Yiying Sun Ziyi Cai Yu Chen Zhongyi Jiang | 2021 | Research2021，，1： | 5 |
| 7 | FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice显示文摘Dear Editor,Animal models,most commonly mice,that lack a protein of interest play an important role in phenotypic and functional studies of a target gene,allowing researchers to answer various biological questions(Chaible et al,2010).At pre-sent,a variety of tools act at the DNA or RNA level to enable researchers to model gene function(and thus protein)deficiency,including nucleic acid based RNA interference(EI-bashir et al.,2001),antisense oligonucleotides(Schoch and Miller,2017),and genome editing-based CRISPR-Cas9(Doudna and Charpentier,2014)strategies.However,challenges remain. | Hongying Gao Chunwei Zheng Jian Du Yue Wu Yonghui Sun Chunsheng Han Kehkooi Kee Yu Rao | 2020 | Protein & Cell2020，11，7： | 5 |
| 8 | Enzymatic synthesis of bioactive compounds by Rhus laccase from Chinese Rhus vernicifera显示文摘A simple one step synthesis of pinoresinol and its derivatives-active components of Du-Zhong(Eu-commia ulmoides) -from coniferyl alcohol and p-courmaryl alcohol with higher yields was achieved by Rhus laccases(RL) catalysis in water miscible organic solvents. Biomacromolecules dehydro-genative polymers(DHP) were only synthesized by fungal laccases,not by RL. The structures and the reaction mechanism were discussed to promote the understanding of the function of laccases in the process of lignin biosynthesis. | AKIYAMA Kazuhiro MIYAKOSHI Tetsuo | 2007 | Science China Chemistry2007，50，2： | 4 |
| 9 | Extraction process of chlorogenic acid in flos lonicerae by enzymatic treatment显示文摘A new method of extracting chlorogenic acid from flos lonicerae, and treating the materials with enzyme before being extracted by ethanol is developed, and the optimum conditions are also investigated in detail. Three important factors, enzyme dosage, treatment time and treatment temperature are adapted to optimize the extraction process. The experimental results show that the extract yield of flos lonicerae and chlorogenic acid can be obviously increased by the cellulase treatment, 61.5 mg chlorogenic acid is obtained from 1.00 g flos lonicerae at most. The optimal temperature of enzymatic treatment is 40 50 ℃. Compared with the use of single cellulase, the combined treatment of cellulase and pectinase increase the extract yield obviously but fail to improve that of chlorogenic acid. | 刘佳佳 赵国玲 王晖 章晓骅 | 2002 | Journal of Central South University of Technology2002，9，4： | 4 |
| 10 | HETEROPHYLLIN-A AND B,TWO CYCLOPEPTIDES,FROM THE ROOTS OF PSEUDOSTELLARIA HETEROPHYLLA显示文摘Two cyclopeptides,heterophyllin A and B,have been isolated from the rootsof Pseudostellaria heterophylla.Their structures were elucidated by chemical,spectroscopic,and enzymatic methods. | Ning Hua TAN Shou Xun ZHAO a Department of Phytochemistry,China Pharmaceutical University,Nanjing,210009 Jun ZHOU Hong Jie ZHANG De Zu WANG Chang Xiang CHEN Xiao Zhu LIU b Laboratory of Phytochemistry,Kunming Institute of Botany,Academia Sinica,Kunming,650204 | 1992 | Chinese Chemical Letters1992，3，8： | 4 |
| 11 | Pretreatment of agricultural residues by supercritical CO_2 at 50–80 °C to enhance enzymatic hydrolysis显示文摘Various agricultural crop residues including corn stover,corn cob,and sorghum stalk with a moisture content of 75 wt%were subjected to a long pretreatment(12–60 h)with supercritical CO_2(scCO_2),at low temperature(50–80°C)and a pressure of 17.5–25.0 MPa.The sugar yields from the enzymatic hydrolysis(EH)of the pretreated samples were as much as three-to fourfold greater than those afforded by the raw materials.However,when pretreatment was conducted within a short time(e.g.0.5 h),as previously reported in the literature,only a slight increase in the EH sugar yields was observed.The proposed sc CO_2pretreatment mechanism demonstrated the role of moisture in the system.Wetting,softening,and swelling were observed to mainly affect the lignocellulose when a suitable amount of water was added.Finally,the samples were analysed by X-ray diffraction and scanning electron microscopy,before and after pretreatment,to investigate the changes in the microscopic structure of the biomass. | Meng-jiao Zhao Qin-qin Xu Guo-min Li Qiao-zhi Zhang Dan Zhou Jian-zhong Yin Hua-shu Zhan | 2019 | Journal of Energy Chemistry2019，28，4： | 3 |
| 12 | The Effect of Hydrolysis with Neutrase on Molecular Weight,Functional Properties,and Antioxidant Activities of Alaska Pollock Protein Isolate显示文摘In this study, the Alaska pollock protein isolate(APPI) was hydrolyzed by Neutrase for 20, 40, 80, 120, 160, 200, and 240 min. Hydrolysates with different molecular weights were produced and they were named as H1–H7. Furthermore, the effects of hydrolysis on the average molecular weights, functional properties(solubility, oil-holding capacities, foaming activities, and emulsifying properties), and antioxidant activities(1, 1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl free radical-scavenging activities) were determined. It was found that when the degree of hydrolysis(DH) increased, the average molecular weights of the hydrolysates decreased significantly. The functional properties of APPI were also significantly improved. The hydrolysates of APPI exhibited better solubility, emulsifying activities, and foaming activities. Hydrolysates with low molecular weights(<1 kDa) had better solubility, oil-holding capacities, and emulsifying activities, while hydrolysates with higher molecular weights(>1 kDa) had better foaming activities. In addition, the hydrolysates exhibited excellent antioxidant properties, while the inhibition values of 1, 1-diphenyl-2-picryl hydroxyl(DPPH), superoxide, and hydroxyl free radical-scavenging activities, were 85.22%, 53.56%, and 75.00% respectively, when the concentration of the hydrolysates was 5.0 mg mL^(-1). The lower the average molecular weight was, the higher was the antioxidant activity. These results indicated that hydrolysis with Neutrase is an effective method for improving the functional and antioxidant properties of APPI. The hydrolysates of APPI displayed great potentials to be used as natural antioxidants in protein-rich aqueous foods such as nutrient supplements and sports beverages. | LIU Chuyi MA Xiaoming CHE Shuai WANG Changwei LI Bafang | 2018 | Journal of Ocean University of China2018，17，6： | 3 |
| 13 | Effects of fruit thinning on ascorbate–glutathione cycle metabolism in black currants(Ribes nigrum L.)显示文摘To elucidate mechanisms regulating ascorbic acid(AsA) biosynthesis and accumulation in the fruit and leaves of black currants,As A and the activities of key enzymes in the ascorbate–glutathione(As A–GSH) cycle were measured from fruit set to fruit ripening during fruit thinning treatments of three common commercial black currant cultivars that differed in their As A levels:'Risager'(low),'Brodtrop'(medium) and 'Adelinia'(high).Treatments were 50% fruit reduction(50% of total fruit set) by hand,control was no thinning.Fruit thinning treatment significantly increased As A content in fruit of all three cultivars from weeks 2 to 8,significantly decreased As A content in leaves from weeks 3 to 8.Dehydroascorbate reductase and monodehydroascorbate reductase activities in fruit and leaves had a similar pattern,increasing during week 2,rose until they peaked in week 4.Ascorbate peroxidase activity in fruit in the thinning treatment was slightly lower than in the control.Fruit thinning was shown to be a good model to test As A biosynthesis regulation and accumulation in black currants.The results from our study provided strong evidence that As A–GSH cycle involved in As A synthesis and accumulation in fruit. | Dong Qin Lijuan Zhao Yu Gary Gao Fangxiao Li Shulei Li Junwei Huo Shuang Lou Peng Liu | 2017 | Journal of Forestry Research2017，28，5： | 3 |
| 14 | Recent advances in proteolysis and peptide/protein separation by chromatographic strategies显示文摘This review gives a broad glance on the progress of recent advances on proteolysis and peptide/protein separation by chroma-tographic strategies in the past ten years, covering the main research in these areas especially in China. The reviewed research focused on enzymatic micro-reactors and peptide separation in bottom-up approaches, and protein and peptide separation in top-down approaches. The new enzymatic micro-reactor is able to accelerate proteolytic reaction rate from conventionally a couple of hours to a few seconds, and the multiple dimensional chromatographic-separation with various models or arrays could sufficiently separate the proteomic mixture. These advances have significantly promoted the research of protein/peptide separation and identification in proteomics. | ZHANG XiangMin1, LIU BaoHong1, ZHANG LiHua2, ZOU HanFa2, CAO Jing1, GAO MingXia1, TANG Jia1, LIU Yun1, YANG PengYuan1 & ZHANG YuKui2 1Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China | 2010 | Science China Chemistry2010，53，4： | 2 |
| 15 | Stoichiometric Conversion of Maltose for Biomanufacturing by In Vitro Synthetic Enzymatic Biosystems显示文摘Maltose is a natural α-(1,4)-linked disaccharide with wide applications in food industries and microbial fermentation. However,maltose has scarcely been used for in vitro biosynthesis, possibly because its phosphorylation by maltose phosphorylase (MP)yields β-glucose 1-phosphate (β-G1P) that cannot be utilized by α-phosphoglucomutase (α-PGM) commonly found in in vitrosynthetic enzymatic biosystems previously constructed by our group. Herein, we designed an in vitro synthetic enzymaticreaction module comprised of MP, β-phosphoglucomutase (β-PGM), and polyphosphate glucokinase (PPGK) for thestoichiometric conversion of each maltose molecule to two glucose 6-phosphate (G6P) molecules. Based on this syntheticmodule, we further constructed two in vitro synthetic biosystems to produce bioelectricity and fructose 1,6-diphosphate (FDP),respectively. The 14-enzyme biobattery achieved a Faraday efficiency of 96.4% and a maximal power density of 0.6mW/cm^(2),whereas the 5-enzyme in vitro FDP-producing biosystem yielded 187.0mM FDP from 50 g/L (139mM) maltose by adopting afed-batch substrate feeding strategy. Our study not only suggests new application scenarios for maltose but also provides novelstrategies for the high-efficient production of bioelectricity and value-added biochemicals. | Guowei Li Xinlei Wei Ranran Wu Wei Zhou Yunjie Li Zhiguang Zhu Chun You | 2022 | BioDesign Research2022，，1： | 2 |
| 16 | A dual crosslinking strategy to tailor rheological properties of gelatin methacryloyl显示文摘3D bioprinting is an emerging technology that enables the fabrication of three-dimensional organised cellular constructs.One of the major challenges in 3D bioprinting is to develop a material to meet the harsh requirements(cellcompatibility,printability,structural stability post-printing and bio-functionality to regulate cell behaviours)suitable for printing.Gelatin methacryloyl(GelMA)has recently emerged as an attractive biomaterial in tissue engineering because it satisfies the requirements of bio-functionality and mechanical tunability.However,poor rheological property such as low viscosity at body temperature inhibits its application in 3D bioprinting.In this work,an enzymatic crosslinking method triggered by Ca2+-independent microbial transglutaminase(MTGase)was introduced to catalyse isopeptide bonds formation between chains of GelMA,which could improve its rheological behaviours,specifically its viscosity.By combining enzymatic crosslinking and photo crosslinking,it is possible to tune the solution viscosity and quickly stabilize the gelatin macromolecules at the same time.The results showed that the enzymatic crosslinking can increase the solution viscosity.Subsequent photo crosslinking could aid in fast stabilization of the structure and make handling easy. | Miaomiao Zhou Bae Hoon Lee Lay Poh Tan | 2017 | International Journal of Bioprinting2017，3，2： | 2 |
| 17 | Enzymatic cyclization of linear peptide to plant cyclopeptide heterophyllin B显示文摘The crude enzyme (PH-1) isolated from Pseudostellaria heterophylla by our group has catalyzed enzymatic cyclization of linear peptide NH2-Gly1-Gly2-Leu-Pro-Pro-Pro-Ile-Phe-COOH (4) into cyclopeptide heterophyllin B (HB) from plant for the first time. To ensure this reaction, some ana-lytical methods including TLC, HPLC, MS, NMR, and 13C labeling were used to prove that the reaction of substrate 4 sharing residue of NH-Phe-Gly-CO was successful. | JIA Aiqun1, LI Xiang2, TAN Ninghua1, LIU Xiaozhu3, SHEN Yuemao1 & ZHOU Jun1 1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Graduate Univer-sity of Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650204, China 2. Chinese Peptide Co., Ltd, Hangzhou 310018, China 3. Southwest Forestry College, Kunming 650204, China | 2006 | Science China Chemistry2006，49，1： | 2 |
| 18 | Implications of denitrification in the ecological status of an urban river using enzymatic activities in sediments as an indicator显示文摘A better understanding of the effects of a number of environmental factors on denitrification is vital for analyzing its role as nitrogen sink and providing deeper knowledge about the ecological status of a nitrate-rich ecosystem. Since few studies have addressed the occurrence and implications of denitrification in river sediments, and complexity of interactions among all these environmental factors makes comprehension of the process difficult, the potential of sediments from the Deba River to attenuate nitrate excess through denitrification was investigated. For this purpose, we adapted an in vitro method to measure activities of two enzymes contributing to the entire multiple-step nitrate reduction: Nitrate Reductase and Nitrite Reductase. The environmental features that influence both or single enzymatic activities were identified as oxygen availability,regulated directly by the moisture content or indirectly through the aerobic respiration,organic matter and nitrate content of sediments, and electrical conductivity and exchangeable sodium percentage of water. Additionally, our results showed that Nitrate Reductase catalyzes the principal limiting step of denitrification in sediments. Therefore,taking this enzymatic activity as an indicator, the southern part of the Deba River catchment presented low potential to denitrify but nitrate-limited sediments, whereas the middle and northern parts were characterized by high denitrification potential but nitraterich sediments. In general, this study on denitrifying enzymatic activities in sediments evaluates the suitability of the management of the effluents from wastewater treatment plants and municipal sewages to ensure a good ecological status of the Deba River. | Jessica Unda-Calvo Miren Martínez-Santos Estilita Ruiz-Romera Juan Luis Lechuga-Crespo | 2019 | Journal of Environmental Sciences2019，31，1： | 2 |
| 19 | Vacuolar invertase genes SbVIN1 and SbVIN2 are differently associated with stem and grain traits in sorghum (Sorghum bicolor)显示文摘In higher plants, vacuolar invertases play essential roles in sugar metabolism, organ development, and sink strength. In sorghum(Sorghum bicolor), two vacuolar invertase genes,Sb VIN1(Sobic. 004 G004800) and Sb VIN2(Sobic. 006 G160700) have been reported, but their enzymatic properties and functional differences are largely unknown. We combined molecular, biochemical and genomic approaches to investigate their roles in sorghum stem and grain traits. Sb VIN1 and Sb VIN2 showed different expression levels in internodes,leaves, and panicles, indicating that their importance in each organ was different. In an in vitro sucrose hydrolysis assay, proteins of both genes heterologously expressed in Pichia pastoris displayed similar enzyme properties including the same optimum reaction p H(5)and similar Kmfor sucroe(49 mmol L-1 and 45 mmol L-1 for Sb VIN1 and Sb VIN2,respectively). The optimum reaction temperatures of Sb VIN1 and Sb VIN2 were 45 °C and65 °C, respectively. Sb VIN2 showed higher tolerance to high temperature than Sb VIN1. We characterized the sequence variation of these two vacuolar invertase genes in a panel of 216 diverse inbred lines of sweet and grain sorghum and performed gene-based association analysis. Sb VIN1 showed significant associations with stem traits including stem length,stem diameter, internode number, stem fresh weight, and Brix, as well as grain traits including hundred-grain weight and grain width. Significantly associated variation sites were mainly in 5′ upstream and intron regions. Sb VIN2 only associated with grain width and stem water-soluble carbohydrates(WSCs) content. We conclude that the vacuolar invertase genes Sb VIN1 and Sb VIN2 are differently associated with stem and grain traits in sorghum. | Yunhua Chi Kimani Wilson Zhiquan Liu Xiaoyuan Wu Li Shang Limin Zhang Haichun Jing Huaiqing Hao | 2020 | The Crop Journal2020，8，2： | 2 |
| 20 | Challenges and perspectives for structural biology of IncRNAs-the example of the Xist IncRNA A-repeats显示文摘Following the discovery of numerous long non-coding RNA(IncRNA)transcripts in the human genome,their important roles in biology and human disease are emerging.Recent progress in experimental methods has enabled the identification of structural features of IncRNAs.However,determining high-resolution structures is challenging as IncRNAs are expected to be dynamic and adopt multiple conformations,which may be modulated by interaction with protein binding partners.The X-inactive specific transcript(Xist)is necessary for X inactivation during dosage compensation in female placental mammals and one of the beststudied IncRNAs.Recent progress has provided new insights into the domain organization,molecular features,and RNA binding proteins that interact with distinct regions of Xist.The A-repeats located at the 5'end of the transcript are of particular interest as they are essential for mediating silencing ofthe inactive X chromosome.Here,we discuss recent progress with elucidating structural features of the Xist IncRNA,focusing on the A-repeats.We discuss the experimental and computational approaches employed that have led to distinct structural models,likely reflecting the intrinsic dynamics of this RNA.The presence of multiple dynamic conformations may also play an important role in the formation ofthe associated RNPs,thus influencing the molecular mechanism underlying the biological function of the Xist A-repeats.We propose that integrative approaches that combine biochemical experiments and high-resolution structural biology in vitro with chemical probing and functional studies in vivo are required to unravel the molecular mechanisms of IncRNAs. | Alisha NJones Michael Sattler | 2019 | Journal of Molecular Cell Biology2019，11，10： | 2 |
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