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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 122-125页

作者： Arne Klungland yun-gui yang Department of Microbiology Division of Diagnostics and InterventionInstitute of Clinical MedicineOslo University Hospital Department of Molecular Medicine Faculty of MedicineInstitute of Basic Medical SciencesUniversity of Oslo CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences

Tomas Lindahl completed his medical studies at Karolinska Institute in ***,his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA *** research is characterized with groundbreaking discoveries on the instability of our genome,the identification of novel DNA repair activities,the characterization of DNA repair pathways,and the association to diseases,throughout his 40 years of scientific career.

关键词： DNA repair completed career instability decay dedicated summary Clare breaking

Base-excision repair and beyond—A short summary attributed to scientific achievements of Tomas Lindahl, Nobel Prize Laureate in Chemistry 2015

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Science China(Life Sciences) 2016年第1期59卷 89-92页

作者： Shuangli Mi Arne Klungland yun-gui yang Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development CAS Center for Excellence in Molecular Cell Science Beijing Institute of Genomics Chinese Academy of Sciences Department of Microbiology Division of Diagnostics and Intervention Institute of Clinical Medicine Oslo University HospitalRikshospitalet Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo

Tomas Lindahl contributed his scientific career to unveiling fundamental mechanisms of DNA decay and repair. He made several ground-breaking discoveries on genome in- stability, novel DNA repair activities and pathway... 详细信息

关键词：碱基切除修复诺贝尔奖得主托马斯科学成果归结化学科学生涯修复机制

Omics Views of Mechanisms for Cell Fate Determination in Early Mammalian Development

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 950-961页

作者： Lin-Fang Ju Heng-Ji Xu yun-gui yang Ying yang Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

During mammalian preimplantation development,a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination,ultimately forming a mature *** with compaction,the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate *** the lineage segregation of the inner cell mass(ICM)and trophectoderm(TE)is the first symbol of cell differentiation,several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages,including the 2-and 4-cell *** underlying mechanisms of early cell fate determination have long been an important research *** this review,we summarize the molecular events that occur during early embryogenesis,as well as the current understanding of their regulatory roles in cell fate ***,as powerful tools for early embryogenesis research,single-cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate ***,we summarize their applications in the research of preimplantation embryos,and provide new insights and perspectives on cell fate regulation.

关键词： Cell fate determination Cellular heterogeneity Cell polarity Single-cell omics Mammalian preimplantation embryo

Characteristics of N^(6)-methyladenosine Modification During Sexual Reproduction of Chlamydomonas reinhardtii

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 756-768页

作者： Ying Lv Fei Han Mengxia Liu Ting Zhang Guanshen Cui Jiaojiao Wang Ying yang yun-gui yang Wenqiang yang Photosynthesis Research Center Key Laboratory of PhotobiologyInstitute of BotanyChinese Academy of SciencesBeijing 100093China China National Botanical Garden Beijing 100093China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100093China

The unicellular green alga Chlamydomonas reinhardtii(hereafter Chlamydomonas)possesses both plant and animal attributes,and it is an ideal model organism for studying fundamental processes such as photosynthesis,sexual reproduction,and life cycle.N^(6)-methyladenosine(m^(6)A)is the most prevalent mRNA modification,and it plays important roles during sexual reproduction in animals and ***,the pattern and function of m^(6)A modification during the sexual reproduction of Chlamydomonas remain ***,we performed transcriptome and methylated RNA immunoprecipitation sequencing(MeRIP-seq)analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life *** results show that m^(6)A modification frequently occurs at the main motif of DRAC(D=G/A/U,R=A/G)in Chlamydomonas ***,m^(6)A peaks in Chlamydomonas mRNAs are mainly enriched in the 30 untranslated regions(30 UTRs)and negatively correlated with the abundance of transcripts at each *** particular,there is a significant negative correlation between the expression levels and the m^(6)A levels of genes involved in the microtubule-associated pathway,indicating that m^(6)A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based *** summary,our findings are the first to demonstrate the distribution and the functions of m^(6)A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m^(6)A modification in the process of sexual reproduction in other plant organisms.

关键词： N6-methyladenosine m^(6)A sequencing Sexual reproduction Microtubule-associated pathway Photosynthesis Chlamydomonas reinhardtii

Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 1014-1029页

作者： Tingfu Du Chunchun Gao Shuaiyao Lu Qianlan Liu yun yang Wenhai Yu Wenjie Li Yong Qiao Sun Cong Tang Junbin Wang Jiahong Gao Yong Zhang Fangyu Luo Ying yang yun-gui yang Xiaozhong Peng National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunming 650118China State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentCollege of Future TechnologyBeijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused the persistent coronavirus disease 2019(COVID-19)pandemic,which has resulted in millions of deaths worldwide and brought an enormous public health and global economic *** recurring global wave of infections has been exacerbated by growing variants of *** this study,the virological characteristics of the original SARS-CoV-2 strain and its variants of concern(VOCs;including Alpha,Beta,and Delta)in vitro,as well as differential transcriptomic landscapes in multiple organs(lung,right ventricle,blood,cerebral cortex,and cerebellum)from the infected rhesus macaques,were *** original strain of SARS-CoV-2 caused a stronger innate immune response in host cells,and its VOCs markedly increased the levels of subgenomic RNAs,such as N,Orf9b,Orf6,and Orf7ab,which are known as the innate immune antagonists and the inhibitors of antiviral ***,the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants ***,a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation-and immune-related ***,peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected ***,these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.

关键词： SARS-CoV-2 Variant of concern Subgenomic RNA Rhesus macaque Transcriptome

RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 850-865页

作者： Boyang Shi Ke An Yueqin Wang Yuhan Fei Caixia Guo Qiangfeng Cliff Zhang yun-gui yang Xin Tian Quancheng Kan Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China MOE Key Laboratory of Bioinformatics Center for Synthetic and Systems BiologyBeijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful ***,the mechanisms that control the resistance of EGFR-TKIs remain largely *** structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain ***,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of *** results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to *** structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and *** study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.

关键词： RNA structure EGFR-TKI resistance Non-small cell lung cancer YRDC ELAVL1

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

NSUN2-mediated mRNA m^(5)C Modification Regulates the Progression of Hepatocellular Carcinoma

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 823-833页

作者： Dan Song Ke An Wenlong Zhai Luyao Feng Yingjie Xu Ran Sun Yueqin Wang yun-gui yang Quancheng Kan Xin Tian Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Digestive Organ Transplantation of Henan Province Zhengzhou UniversityZhengzhou 450052China

RNA modifications affect many biological processes and physiological *** 5-methylcytosine(m^(5)C)modification regulates the progression of multiple ***,its characteristics and functions in hepatocellular carcinoma(HCC)remain largely ***,we found that HCC tissues had a higher m^(5)C methylation level than the adjacent normal *** analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways,such as the Ras and PI3K-Akt *** m^(5)C methyltransferase NSUN2 was highly expressed in HCC ***,the expression of many genes was positively correlated with the expression of NSUN2,including GRB2,RNF115,AATF,ADAM15,RTN3,and ***-time PCR assays further revealed that the expression of the mRNAs of GRB2,RNF115,and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC ***,NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling ***,knocking down NSUN2 caused cell cycle *** together,our study demonstrates the vital role of NSUN2 in the progression of HCC.

关键词： 5-methylcytosine Hepatocellular carcinoma NSUN2 Ras pathway Sorafenib

m^6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2

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Genomics, Proteomics & Bioinformatics 2019年第2期17卷 154-168页

作者： Junchen Chen Yi-Chang Zhang Chunmin Huang Hui Shen Baofa Sun Xuejun Cheng Yu-Jie Zhang yun-gui yang Qiang Shu Ying yang Xuekun Li The Children's Hospital School of Medicine Zhejiang University Hangzhou 310052 China The Institute of Translational Medicine School of Medicine Zhejiang University Hangzhou 310029 China CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Sino-Danish College University of Chinese Academy of Sciences Beijing 101408 China Institute of Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China

N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.

关键词： N6-methyladenosine (m6A) Mettl3 Neurogenesis Neuronal development Ezh2

N^6 -methyl-adenosine (m^6 A) in RNA: An Old Modification with A Novel Epigenetic Function

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Genomics, Proteomics & Bioinformatics 2013年第1期11卷 8-17页

作者： Yamei Niu Xu Zhao Yong-Sheng Wu Ming-Ming Li Xiu-Jie Wang yun-gui yang Disease Genomics and Individualized Medicine Laboratory Beijing Institute of GenomicsChinese Academy of Sciences University of Chinese Academy of Sciences Institute of Genetics and Developmental Biology Chinese Academy of Sciences

N6-methyl-adenosine （m6A） is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation ofm6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 （METTL3）. m6A modification on messenger RNAs （mRNAs） mainly occurs in the exonic regions and 3＇-untranslated region （3＇-UTR） as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity- associated （FTO） gene and ALKBH5, which catalyze m6A demethylation in an cx-ketoglutarate （a-KG）- and FeZ ＋ -dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from devel- opment and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role ofm6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.

关键词： N6-methyl-adenosineMETTL3 FTO ALKBH5 RNA metabolism