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基因组蛋白质组与生物信息学报(英文版)
基因组蛋白质组与生物信息学报(英文版)

杨焕明;于军

双月刊

1672-0229

journal@cspg.net

010-84097425

100101

北京市朝阳区北辰西路1-7号中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)/Journal Genomics、Proteomics & BioinformaticsCSCDCSTPCD北大核心SCI
查看更多>>Genomics, Proteomics & Bioinformatics (《基因组蛋白质组与生物信息学报》,简称GPB)创刊于2003年,是由中国科学院北京基因组研究所主办、科学出版社出版的国家级英文学术期刊,由杨焕明教授、于军教授担任主编,汪建教授、贺福初院士担任副主编。 本刊主要刊载基因组学、蛋白质组学、生物信息学及其相关领域的研究进展、综述、研究论文、实验技术与方法、研究快讯等高质量的稿件,突出刊物的学术性、前沿性、指导性和实用性。 本刊读者对象为基础医学、生命科学、农学、计算机科学领域的科研与教学人员、研究生等,以及数学、物理学领域对生物科学有兴趣的研究者。 GPB (ISSN 1672-0229,CN11-4926/Q)现为季刊,面向国内外发行,邮发代号80-113。2004年国内定价每期45元,全年180元。 欢迎赐稿和订阅! 联系人:张欣 《基因组蛋白质组与生物信息学报》编辑部 北京空港科技创业园B区6号 101300 Tel: 010-80485179 Fax: 010-80498676 E-mail:editor@genomics.org.cn Http:
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    RNA Modifications and Epitranscriptomics

    Chengqi YiJianhua Yang
    675-677页

    m6A-TSHub:Unveiling the Context-specific m6A Methylation and m6A-affecting Mutations in 23 Human Tissues

    Bowen SongDaiyun HuangYuxin ZhangZhen Wei...
    678-694页
    查看更多>>摘要:As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs(lncRNAs),N6-methyladenosine(m6A)RNA methylation has been shown to participate in essential biological processes.Recent studies have revealed the distinct patterns of m6A methylome across human tissues,and a major challenge remains in elucidating the tissue-specific presence and cir-cuitry of m6A methylation.We present here a comprehensive online platform,m6A-TSHub,for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark.m6A-TSHub consists of four core components,including(1)m6A-TSDB,a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tis-sues and 499,369 m6A sites from 25 tumor conditions,respectively;(2)m6A-TSFinder,a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences,which was constructed using multi-instance deep neural networks with gated attention;(3)m6A-TSVar,a web server for assessing the impact of genetic variants on tissue-specific m6A RNA mod-ifications;and(4)m6A-CAVar,a database of 587,983 The Cancer Genome Atlas(TCGA)cancer mutations(derived from 27 cancer types)that were predicted to affect m6A modifications in the pri-mary tissue of cancers.The database should make a useful resource for studying the m6A methy-lome and the genetic factors of epitranscriptome disturbance in a specific tissue(or cancer type).m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.

    N6-methyladenosine and Its Implications in Viruses

    Yafen WangXiang Zhou
    695-706页
    查看更多>>摘要:N6-methyladenine(m6A)is the most abundant RNA modification in mammalian mes-senger RNAs(mRNAs),which participates in and regulates many important biological activities,such as tissue development and stem cell differentiation.Due to an improved understanding of m6A,researchers have discovered that the biological function of m6A can be linked to many stages of mRNA metabolism and that m6A can regulate a variety of complex biological processes.In addi-tion to its location on mammalian mRNAs,m6A has been identified on viral transcripts.m6A also plays important roles in the life cycle of many viruses and in viral replication in host cells.In this review,we briefly introduce the detection methods of m6A,the m6A-related proteins,and the func-tions of m6A.We also summarize the effects of m6A-related proteins on viral replication and infec-tion.We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses,and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication.We also anticipate that this review can stimulate collaborative research from different fields,such as chemistry,biology,and medicine,and promote the development of antiviral drugs and vaccines.

    Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma

    Yixian CunSanqi AnHaiqing ZhengJing Lan...
    707-728页
    查看更多>>摘要:Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m6A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m6A methylation.We then indicate that SRSF7 is a novel m6A regulator,which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase com-plex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase.The two m6A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recog-nition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal-and spatial-specific regulation of m6A mediated by RNA-binding proteins(RBPs).

    Transcriptome-wide Dynamics of m6A mRNA Methylation During Porcine Spermatogenesis

    Zidong LiuXiaoxu ChenPengfei ZhangFuyuan Li...
    729-741页
    查看更多>>摘要:Spermatogenesis is a continual process that occurs in the testes,in which diploid sper-matogonial stem cells(SSCs)differentiate and generate haploid spermatozoa.This highly efficient and intricate process is orchestrated at multiple levels.N6-methyladenosine(m6A),an epigenetic modification prevalent in mRNAs,is implicated in the transcriptional regulation during spermato-genesis.However,the dynamics of m6A modification in non-rodent mammalian species remains unclear.Here,we systematically investigated the profile and role of m6A during spermatogenesis in pigs.By analyzing the transcriptomic distribution of m6A in spermatogonia,spermatocytes,and round spermatids,we identified a globally conserved m6A pattern between porcine and murine genes with spermatogenic function.We found that m6A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators.In addition,transcriptomes in porcine male germ cells could be subjected to the m6A modification.Our data show that m6A plays the reg-ulatory roles during spermatogenesis in pigs,which is similar to that in mice.Illustrations of this point are three genes(SETDB1,FOXO1,and FOXO3)that are crucial to the determination of the fate of SSCs.To the best of our knowledge,this study for the first time uncovers the expression profile and role of m6A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.

    m6A Profile Dynamics Indicates Regulation of Oyster Development by m6A-RNA Epitranscriptomes

    Lorane Le FrancBruno PettonPascal FavrelGuillaume Rivière...
    742-755页
    查看更多>>摘要:The N6-methylation of RNA adenosines(N6-methyladenosine,m6A)is an important reg-ulator of gene expression with critical implications in vertebrate and insect development.However,the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown.Using methylated RNA immunoprecipitation sequencing(MeRIP-seq),we generated transcriptome-wide m6A-RNA methylomes covering the entire development of the oyster from oocytes to juveniles.Oyster RNA classes display specific m6A signatures,with messenger RNAs(mRNAs)and long non-coding RNAs(lncRNAs)exhibiting distinct profiles and being highly methy-lated compared to transposable element(TE)transcripts.Epitranscriptomes are dynamic and corre-spond to the chronological steps of development(cleavage,gastrulation,organogenesis,and metamorphosis),with minimal mRNA and IncRNA methylation at the morula stage followed by a global increase.mRNA m6A levels are correlated with transcript levels,and shifts in methylation pro-files correspond to expression kinetics.Differentially methylated transcripts cluster according to em-bryo-larval stages and bear the corresponding developmental functions(cell division,signal transduction,morphogenesis,and cell differentiation).The m6A level of TE transcripts is also regu-lated and peaks during the gastrulation.We demonstrate that m6A-RNA methylomes are dynamic and associated with gene expression regulation during oyster development.The putative epitranscrip-tome implication in the cleavage,maternal-to-zygotic transition,and cell differentiation in a lophotro-chozoan model brings new insights into the control and evolution of developmental processes.

    Characteristics of N6-methyladenosine Modification During Sexual Reproduction of Chlamydomonas reinhardtii

    Ying LvFei HanMengxia LiuTing Zhang...
    756-768页
    查看更多>>摘要:The unicellular green alga Chlamydomonas reinhardtii(hereafter Chlamydomonas)pos-sesses both plant and animal attributes,and it is an ideal model organism for studying fundamental processes such as photosynthesis,sexual reproduction,and life cycle.N6-methyladenosine(m6A)is the most prevalent mRNA modification,and it plays important roles during sexual reproduction in ani-mals and plants.However,the pattern and function of m6A modification during the sexual repro-duction of Chlamydomonas remain unknown.Here,we performed transcriptome and methylated RNA immunoprecipitation sequencing(MeRIP-seq)analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle.The results show that m6A modifica-tion frequently occurs at the main motif of DRAC(D=G/A/U,R=A/G)in Chlamydomonas mRNAs.Moreover,m6A peaks in Chlamydomonas mRNAs are mainly enriched in the 3'untrans-lated regions(3'UTRs)and negatively correlated with the abundance of transcripts at each stage.In particular,there is a significant negative correlation between the expression levels and the m6A levels of genes involved in the microtubule-associated pathway,indicating that m6A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based movement.In summary,our findings are the first to demonstrate the distribu-tion and the functions of m6A modification in Chlamydomonas mRNAs and provide new evolution-ary insights into m6A modification in the process of sexual reproduction in other plant organisms.

    RNA Methylome Reveals the m6A-mediated Regulation of Flavor Metabolites in Tea Leaves under Solar-withering

    Chen ZhuShuting ZhangChengzhe ZhouCaiyun Tian...
    769-787页
    查看更多>>摘要:The epitranscriptomic mark N6-methyladenosine(m6A),which is the predominant inter-nal modification in RNA,is important for plant responses to diverse stresses.Multiple environmen-tal stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor.However,the effects of the m6A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized.We performed an integrated RNA methylome and transcriptome analysis to explore the m6A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea(Camellia sinensis)leaves under solar-withering conditions.Dynamic changes in global m6A level in tea leaves were mainly controlled by two m6A erasers(CsALKBH4A and CsALKBH4B)during solar-withering treatments.Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways.Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid,catechin,and theaflavin contents by triggering alternative splicing-mediated regulation.Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m6A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.

    Identifying RNA Modifications by Direct RNA Sequencing Reveals Complexity of Epitranscriptomic Dynamics in Rice

    Feng YuHuanhuan QiLi GaoSen Luo...
    788-804页
    查看更多>>摘要:Transcriptome analysis based on high-throughput sequencing of a cDNA library has been widely applied to functional genomic studies.However,the cDNA dependence of most RNA sequencing techniques constrains their ability to detect base modifications on RNA,which is an important element for the post-transcriptional regulation of gene expression.To comprehen-sively profile the N6-methyladenosine(m6A)and N6-methylcytosine(m5C)modifications on RNA,direct RNA sequencing(DRS)using the latest Oxford Nanopore Technology was applied to analyze the transcriptome of six tissues in rice.Approximately 94 million reads were generated,with an average length ranging from 619 nt to 1013 nt,and a total of 45,707 transcripts across 34,763 genes were detected.Expression profiles of transcripts at the isoform level were quantified among tissues.Transcriptome-wide mapping of m6A and m5C demonstrated that both modifications exhibited tissue-specific characteristics.The transcripts with m6A modifications tended to be modified by m5C,and the transcripts with modifications presented higher expression levels along with shorter poly(A)tails than transcripts without modifications,suggesting the complexity of gene expression regulation.Gene Ontology analysis demonstrated that m6A-and m5C-modified transcripts were involved in central metabolic pathways related to the life cycle,with modifications on the target genes selected in a tissue-specific manner.Furthermore,most modified sites were located within quantitative trait loci that control important agronomic traits,highlighting the value of cloning functional loci.The results provide new insights into the expression regulation complexity and data resource of the transcriptome and epitranscriptome,improving our understanding of the rice gen-ome.

    Dynamic DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine Reprogramming During Early Human Development

    Xiao HanJia GuoMengke WangNan Zhang...
    805-822页
    查看更多>>摘要:After implantation,complex and highly specialized molecular events render functionally distinct organ formation,whereas how the epigenome shapes organ-specific development remains to be fully elucidated.Here,nano-hmC-Seal,RNA bisulfite sequencing(RNA-BisSeq),and RNA sequencing(RNA-Seq)were performed,and the first multilayer landscapes of DNA 5-hydroxymethylcytosine(5hmC)and RNA 5-methylcytosine(m5C)epigenomes were obtained in the heart,kidney,liver,and lung of the human foetuses at 13-28 weeks with 123 samples in total.We identified 70,091 and 503 organ-and stage-specific differentially hydroxymethylated regions(DhMRs)and m5C-modified mRNAs,respectively.The key transcription factors(TFs),T-box transcription factor 20(TBX20),paired box 8(PAX8),krueppel-like factor 1(KLF1),transcription factor 21(TCF21),and CCAAT enhancer binding protein beta(CEBPB),specifically contribute to the formation of distinct organs at different stages.Additionally,5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes.Our integrated studies reveal a putative essential link between DNA modification and RNA methylation,and illustrate the epige-netic maps during human foetal organogenesis,which provide a foundation for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.