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Dynamic RNA methylation modifications and their regulatory role in mammalian development and diseases

Science China(Life Sciences) 2024年第10期67卷 2084-2104页

作者： Wenlan Yang yongliang zhao Yungui Yang State Key Laboratory of Reproductive Regulation&Breeding of Grassland Livestock Inner Mongolia Key Laboratory for Molecular Regulation of the CellSchool of Life SciencesInner Mongolia UniversityHohhot 010020China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China

Among over 170 different types of chemical modifications on RNA nucleobases identified so far,RNA methylation is the major type of epitranscriptomic modifications existing on almost all types of RNAs,and has been demonstrated to participate in the entire process of RNA metabolism,including transcription,pre-mRNA alternative splicing and maturation,mRNA nucleus export,mRNA degradation and stabilization,mRNA *** to the development of high-throughput detection technologies and the identification of both dynamic regulators and recognition proteins,mechanisms of RNA methylation modification in regulating the normal development of the organism as well as various disease occurrence and developmental abnormalities upon RNA methylation dysregulation have become increasingly ***,we particularly focus on three types of RNA methylations:N^(6)-methylcytosine(m^(6)A),5-methylcytosine(m^(5)C),and N^(7)-methyladenosine(m^(7)G).We summarize the elements related to their dynamic installment and removal,specific binding proteins,and the development of high-throughput detection ***,for a comprehensive understanding of their biological significance,we also overview the latest knowledge on the underlying mechanisms and key roles of these three mRNA methylation modifications in gametogenesis,embryonic development,immune system development,as well as disease and tumor progression.

关键词： RNA methylation(m^(6)A m5C and m7G) detection techniques RNA metabolism gametogenesis embryogenesis immune system development tumorigenesis

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Optimization of cold-end system of thermal power plants based on entropy generation minimization

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Frontiers in Energy 2022年第6期16卷 956-972页

作者： Yue FU yongliang zhao Ming LIU Jinshi WANG Junjie YAN State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong UniversityXi’an 710049China

Cold-end systems are heat sinks of thermal power cycles,which have an essential effect on the overall performance of thermal power *** enhance the efficiency of thermal power plants,multi-pressure condensers have been applied in some large-capacity thermal power ***,little attention has been paid to the optimization of the cold-end system with multi-pressure condensers which have multiple parameters to be ***,the design optimization methods of coldend systems with single-and multi-pressure condensers are developed based on the entropy generation rate,and the genetic algorithm(GA)is used to optimize multiple *** parameters,including heat transfer area of multi-pressure condensers,steam distribution in condensers,and cooling water mass flow rate,are optimized while considering detailed entropy generation rate of the cold-end *** results show that the entropy generation rate of the multi-pressure cold-end system is less than that of the single-pressure cold-end system when the total condenser area is ***,the economic performance can be improved with the adoption of the multi-pressure cold-end *** compared with the single-pressure cold-end system,the excess revenues gained by using dual-and quadruplepressure cold-end systems are 575 and 580 k$/a,respectively.

关键词： cold-end system entropy generation minimization optimization economic analysis genetic algorithm(GA)

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The Scavenging of Free Radical and Oxygen Species Activities and Hydration Capacity of Collagen Hydrolysates from Walleye Pollock(Theragra chalcogramma) Skin

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Journal of Ocean University of China 2009年第2期8卷 171-176页

作者： ZHUANG yongliang LI Bafang zhao Xue College of Food Science and Engineering Ocean University of China Qingdao 266003 P. R. China

Fish skin collagen hydrolysates （FSCH） were prepared from walleye pollock （Theragra chalcogramrna） using a mixture of enzymes, namely trypsin and flavourzyme. The degree of hydrolysis of the skin collagen was 27.3%. FSCH was mainly composed of low-molecular-weight peptides and the relative proportion of 〈1000Da fraction was 70.6%. Free radical and oxygen species scavenging activities of FSCH were investigated in four model systems, including diphenylpicrylhy-drazyl radical （DPPH）, superoxide anion radical, hydroxyl radical and hydrogen peroxide model, and compared with that of a native antioxidant, reduced glutathione （GSH）. FSCH was also evaluated by water-absorbing and water-holding capacity. The results showed that FSCH was able to scavenge free radical and oxygen species significantly and to enhance water-absorbing and water-holding capacity remarkably. Therefore FSCH may have potential applications in the medicine and food industries.

关键词： walleye pollock collagen free radical-scavenging activity water-holding capacity

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Fluorescence enhancement of Tb^(3+) complexes by adding silica-coated silver nanoparticles

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Science China Chemistry 2015年第6期58卷 979-985页

作者： Dan Zhou Xuemei Lin Ailing Wang Jingjing Li Yanrong Qu Haibin Chu yongliang zhao College of Chemistry and Chemical Engineering Inner Mongolia University

Six kinds of terbium ternary complexes with halo-benzoic acids were synthesized. Their compositions were determined by C, H elemental analyzer and EDTA titration. The infrared spectra, ultraviolet absorption spectra, and fluorescence spectra were also measured to identify the complexes. Elemental analysis showed that the compositions of these complexes were Tb（p-BrBA）3- H20, Tb（p-CIBA）3- 2H20, Tb（p-FBA）3- H20, Tb（o-FBA）3·2H20, Tb（o-CIBA）3· H20, and Tb（o-BrBA）3. H20, respectively. The monodispersed Ag@SiO2 core-shell nanoparticles with silica thicknesses of 10, 15, and 25 nm were success- fully prepared and characterized by transmission-electron microscopy. Fluorescence intensities of the complexes were detected before and after Ag@SiO2core-shell nanoparticles were added; the enhancement times were related to the silica-shell thick- ness. The fluorescence enhancement times were largest when the thickness of the silica shell was 25 nm. The mechanism may be attributed to the localized surface-plasmon resonance. Furthermore, the enhancement effect of terbium fluoro-benzoate complexes was the strongest in these complexes. This result may be attributed to the hydrogen bond between the hydroxyl on the surface of the silica shell and the fluorine atom.

关键词： Tb3+ complexes halobenzoic acids Ag@SiO2 core-shell nanoparticles metal-enhanced fluorescence

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Regulation of U6 Promoter Activity by Transcriptional Interference in Viral Vector-Based RNAi

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Genomics, Proteomics & Bioinformatics 2010年第3期8卷 170-179页

作者： Linghu Nie Meghna Das Thakur Yumei Wang Qin Su yongliang zhao Yunfeng Feng Key Laboratory of Genome Sciences and Information Cancer Biology and Genetics Group Beijing Institute of Genomics Chinese Acadamy of Sciences Beijing 100029 China Departments of Medicine and Cell Biology Washington University St. Louis MO 63110 USA Immunocore Limited Abingdon Oxon OX14 4RX UK.

The direct negative impact of the transcriptional activity of one component on the second one in c/s is referred to as transcriptional interference （TI）. U6 is a type III RNA polymerase III promoter commonly used for driving small hairpin RNA （shRNA） expression in vector-based RNAi. In the design and construction of viral vectors, multiple transcription units may be arranged in close proximity in a space-limited vector. Determining if U6 promoter activity can be affected by TI is critical for the expression of target shRNA in gene therapy or loss-of-function studies. In this research, we designed and implemented a modified retroviral system where shRNA and exogenous gene expressions were driven by two independent transcriptional units. We arranged U6 promoter driving .shRNA expression and UbiC promoter in two promoter arrangements. In primary macrophages, we found U6 promoter activity was inhibited by UbiC promoter when in the divergent arrangement but not in tandem. In contrast, PKG promoter had no such negative impact. Instead of enhancing U6 promoter activity, CMV enhancer had significant negative impact on U6 promoter activity in the presence of UbiC promoter. Our results indicate that U6 promoter activity can be affected by TI in a proximal promoter-specific and arrange- ment-dependent manner.

关键词： transcriptional interference U6 promoter shRNA retrovirus

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A Multifunctional Lentiviral-Based Gene Knockdown with Concurrent Rescue that Controls for Off-Target Effects of RNAi

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Genomics, Proteomics & Bioinformatics 2010年第4期8卷 238-245页

作者： Yunfeng Feng Linghu Nie Meghna Das Thakur Qin Su Zhenfen Chi yongliang zhao Gregory D. Longmore Departments of Medicine and Cell Biology Washington University St. Louis MO 63110 USA Key Laboratory of Genome Sciences and Information Cancer Biology and Genetics Group Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Immunocore Limited Abingdon Oxon OX14 4RX UK

The efficient, stable delivery of siRNA into cells, and the appropriate controls for non-specific off-target effects of siRNA are major limitations to functional studies using siRNA technology. To overcome these drawbacks, we have developed a single lentiviral vector that can concurrently deplete endogenous gene expression while expressing an epitope-tagged siRNA-resistant target gene in the same cell. To demonstrate the functional utility of this system, we performed RNAi-depleted α-actinin-1 （α-ACTN1） expression in human T cells. α-ACTN1 RNAi resulted in inhibited chemotaxis to SDF-1α, but it can be completely rescued by concurrent expression of RNAi-resistant α-ACTN1 （rr-α-ACTN1） in the same cell. The presence of a GFP tag on rr-α-ACTN1 allowed for detection of appropriate subcellular localization of rr-α-ACTN1. This system provides not only an internal control for RNAi off-target effects, but also the potential tool for rapid structure-function analyses and gene therapy.

关键词： lentivirus RNAi shRNA α-actinin-1 chemotaxis

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A Multi-Parameter Sensor Based on Cascaded Photonic Crystal Cavities Filled with Magnetic Fluid

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Optics and Photonics Journal 2020年第7期10卷 183-196页

作者： yongliang zhao Delong Su Yongxi Li College of Science University of Shanghai for Science and Technology Shanghai China

A kind of photonic crystal (PC) micro-cavity sensor based on magnetic fluid (MF) filling is designed with simulation model. Generally, many sensors’ designs are based on a universal temperature in the whole structure. However, strong photothermal effect in high Q micro-cavities will lead to different temperatures between cavities and environment inevitably. In many theoretical PC sensor designs, researchers neglected the different temperature between environment and cavities. This simple hypothesis will probably lead to failure of sensor design and get wrong temperature. Moreover, few theoretical or experimental works have been done to study optical cavity’s heating process and temperature. We propose that researchers should take seriously about this point. Here, the designed cascaded micro-cavity structure has three spectral lines and a reversible sensitivity matrix, which can simultaneously detect magnetic field, ambient temperature and MF micro-cavity temperature. It can solve the magnetic field and temperature cross-sensitivity problem, and further, distinguish the different temperatures of environment and magnetic fluid cavities. The influence of hole radius and slab thickness on the depth and Q value of the resonant spectral line are also studied. Responses of three dips to magnetic field, ambient temperature and MF micro-cavity temperature are simulated, respectively, where dip 1 belongs to MF cavity 1, dip 2 and dip 3 belong to MF cavity 2. The obtained magnetic field sensitivities are 2.89 pm/Oe, 4.57 pm/Oe, and 5.14 pm/Oe, respectively;the ambient temperature sensitivities are 65.51 pm/K, 50.94 pm/K, and 58.98 pm/K, respectively;and the MF micro-cavity temperature sensitivities are −14.41 pm/K, −17.06 pm/K, and −18.81 pm/K, respectively.

关键词： Magnetic Field Sensing Magnetic Fluid Micro-Cavity Photonic Crystal Temperature Sensing

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Epitranscriptomic 5-Methylcytosine Profile in PM_(2.5)-induced Mouse Pulmonary Fibrosis

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Genomics, Proteomics & Bioinformatics 2020年第1期18卷 41-51页

作者： Xiao Han Hanchen Liu Zezhong Zhang Wenlan Yang Chunyan Wu Xueying Liu Fang Zhang Baofa Sun yongliang zhao Guibin Jiang Yun-Gui Yang Wenjun Ding College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentCollege of Future TechnologyBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Exposure of airborne particulate matter(PM)with an aerodynamic diameter less than 2.5μm(PM2.5)is epidemiologically associated with lung dysfunction and respiratory symptoms,including pulmonary ***,whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly ***,using a PM2.5-induced pulmonary fibrosis mouse model,we found that PM2.5 exposure leads to aberrant mRNA5-methylcytosine(m5C)gain and loss in fibrotic lung ***,we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 *** genes act as m5C gain-upregulated factors,probably critical for the development of PM2.5-induced fibrosis in mouse *** genes,including Lcn2,Mmp9,Chi3l1,Adipoq,Atp5j2,Atp5l,Atpif1,Ndufb6,Fgr,Slc11 a1,and Tyrobp,are highly related to oxidative stress response,inflammatory responses,and immune system *** study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

关键词： PM2.5 exposure mRNA m^5C Pulmonary fibrosis Inflammation Immune response

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Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

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Chinese Medical Journal 2014年第9期127卷 1645-1650页

作者： Fang Hongbo Liu Jing Guo Dan Liu Peixiang zhao yongliang Center for Genome Variations and Precision Bio-Medicine Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Center for Genome Variations and Precision Bio-Medicine Beijing Institute of Genomics University of Chinese Academy of Sciences Beijing 100049 China Department of Clinical Laboratory First People's Hospital of Yueyang Yueyang Hunan 414000 China

Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological *** hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI *** this study,we used a methylation-specific PCR （MSP） method to evaluate the methylation status of the TGFBI promoter in human *** Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical *** DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP *** Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines ***,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia *** The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.

关键词： TGFBI leukemia methylation-specific PCR hypermethylation

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GPR54 deficiency reduces the Treg population and aggravates experimental autoimmune encephalomyelitis in mice

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Science China(Life Sciences) 2018年第6期61卷 675-687页

作者： Roumei Xing Fang Liu Yiqing Yang Xueqin Cui Tongtong Wang Ling Xie yongliang zhao Lei Fang Tingfang Yi Biao Zheng Mingyao Liu Huaqing Chen Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Third Venture Biotechnology Co. Ltd. Institute of Biosciences and Technology Department of Molecular and Cellular Medicine Texas A&M University Health Science Center

GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54^(-/-) mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54^(-/-) mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis(EAE) developed in the Gpr54^(-/-) mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54^(-/-) mice compared to the respective wild-type control,suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.

关键词： GPR54 T cells regulatory T cells experimental autoimmune encephalomyelitis knockout mice

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