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1Extensive translation of circular RNAs driven by N6-methyladenosine显示文摘广泛的 pre-mRNA 拼接背在人的 transcriptome 产生众多的圆形的 RNA (circRNAs ) 。然而,这些 circRNAs 的生物功能仍然保持大部分不清楚。这里,我们报导那 N 6-methyladenosine (m 6 一) , RNA 的最丰富的基础修正,在人的房间从 circRNAs 支持蛋白质翻译的有效开始。我们发现那一致 m 6 A 主题在 circRNAs 和单个 m 6 一个地点是足够的驾驶翻译开始。这 m 6A 驱动的翻译要求开始因素 eIF4G2 和 m 6 读者 YTHDF3,并且被 methyltransferase METTL3/14 提高,在热吃惊之上由 demethylase FTO,和 upregulated 禁止了。通过介绍的 polysome 的进一步的分析,计算预言和集体 spectrometry 揭示那 m 6 circRNAs 的 A 驱动的翻译是普遍的,与有翻译潜力的几百内长的 circRNAs。我们的学习扩展人的 transcriptome 的编码风景,并且在对环境应力的细胞的回答建议导出 circRNA 的蛋白质的一个角色。Yun Yang Xiaojuan Fan Miaowei Mao Xiaowei Song Ping Wu6,7 Yang Zhang Yongfeng Jin Yi Yang Ling-Ling Chen Yang Wang Catherine CL Wong Xinshu Xiao Zefeng Wang 2017Cell Research2017,27,5:246
2Ythdc2 is an N^6-methyladenosine binding protein that regulates mammalian spermatogenesis显示文摘N 6-methyladenosine (m 6 一) 是在真核细胞的 mRNA 的最普通的内部修正。它动态地被安装并且搬迁,并且充当 mRNA 新陈代谢,包括干细胞 pluripotency 的调整生物过程,房间区别,和精力动态平衡的新层。m 6 A 被选择有约束力的蛋白质认出;YTHDF1 和 YTHDF3 在音乐会工作影响 m 6包含 A 的 mRNAs, YTHDF2 帮助 mRNA 腐烂,和 YTHDC1 影响它的目标的原子处理。YTHDC2 的生物功能, YTH 蛋白质家庭,的最后的成员仍然保持未知。我们报导 YTHDC2 有选择地绑 m 6 在它的一致主题的 A。YTHDC2 提高它的目标的翻译效率并且也减少他们的 mRNA 丰富。Ythdc2 猛烈老鼠是不肥沃的;男性们让显著地更小的睾丸和女性同窝出生的人与那些相比有显著地更小的卵巢。Ythdc2 猛烈老鼠的细菌房间不经过 zygotene 阶段发展,因此,当成熟分裂开始, Ythdc2 是在睾丸的 upregulated。因此, YTHDC2 是 m 6 在精子发生期间起关键作用的 A 绑定蛋白质。Phillip J Hsu Yunfei Zhu Honghui Ma Yueshuai Guo Xiaodan Shi Yuanyuan Liu Meijie Qi Zhike Lu Hailing Shi Jianying Wang Yiwei Cheng Guanzheng Luo Qing Dai Mingxi Liu Xuejiang Guo Jiahao Sha Bin Shen Chuan He 2017Cell Research2017,27,9:96
3Dynamic transcriptomic m^6A decoration: writers, erasers, readers and functions in RNA metabolism显示文摘Ying Yang Phillip J. Hsu Yu-Sheng Chen Yun-Gui Yang 2018Cell Research2018,28,6:99
4Mettl3-mediated m ^6A regulates spermatogonial differentia- tion and meiosis initiation显示文摘METTL3 催化 N 6-methyl-adenosine 的形成(m 6 一) 它在调整各种各样的生物过程有重要角色。然而,在里面 Mettl3 的 vivo 功能在哺乳动物仍然保持大部分未知。这里,我们产生了细菌房间特定的 Mettl3 猛烈老鼠并且证明 Mettl3 为男富饶和精子发生是必要的。在细菌房间的 Mettl3 的脱离严重地禁止了 spermatogonial 区别并且堵住了成熟分裂的开始。Transcriptome 和 m 6 介绍分析表明在精子发生工作的基因改变了表示并且其他的拼接的侧面。我们的调查结果提供新奇卓见进功能和调停 Mettl3 的 m 6 在精子发生的修正和在哺乳动物的复制。Kai Xu Ying- Yang Gui-Hai Feng Bao-Fa Sun Jun-Qing Chen Yu-Fei Li Yu-Sheng Chen Xin-Xin Zhang Chen-Xin Wang Li-Yuan Jiang Chao Liu Ze-Yu Zhang Xiu-Jie Wang Qi Zhou Yun-Gui Yang Wei Li 2017Cell Research2017,27,9:53
5RNA N^6-methyladenosine modification in cancers: current status and perspectives显示文摘Xiaolan Deng Rui Su Hengyou Weng Huilin Huang Zejuan Li Jianjun Chen 2018Cell Research2018,28,5:55
6A novel m6A reader Prrc2a controls oligodendroglial specification and myelination显示文摘While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.Rong Wu Ang Li Baofa Sun Jian-Guang Sun Jinhua Zhang Ting Zhang Yusheng Chen Yujie Xiao Yuhao Gao Qingyang Zhang Jun Ma Xin Yang Yajin Liao Wei-Yi Lai Xiaolong Qi Shukun Wang Yousheng Shu Hai-Lin Wang Fengchao Wang Yun-Gui Yang Zengqiang Yuan 2019Cell Research2019,29,1:32
7The role of m6A modification in the biological functions and diseases显示文摘N6-methyladenosine(m6A)is the most prevalent,abundant and conserved internal cotranscriptional modification in eukaryotic RNAs,especially within higher eukaryotic cells.m6A modification is modified by the m6A methyltransferases,or writers,such as METTL3/14/16,RBM15/15B,ZC3H3,VIRMA,CBLL1,WTAP,and KIAA1429,and,removed by the demethylases,or erasers,including FTO and ALKBH5.It is recognized by m6A-binding proteins YTHDF1/2/3,YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1,also known as'readers'.Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions,especially in the initiation and progression of different types of human cancers.In this review,we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic,central nervous and reproductive systems.We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation,its regulators and downstream target genes,during cancer progression in above systems.We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.Xiulin Jiang Baiyang Liu Zhi Nie Lincan Duan Qiuxia Xiong Zhixian Jin Cuiping Yang Yongbin Chen 2021Signal Transduction and Targeted Therapy2021,6,3:16
8Aberrant expression of enzymes regulating m^6A mRNA methylation: implication in cancer显示文摘N^6-methyladenosine(m^6 A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal,cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m^6 A methylation has been implicated in the development and maintenance of diverse human cancers. Altered m^6 A levels affect RNA processing, mRNA degradation, and translation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studies have reported that the abnormal expression of m^6 A regulatory enzymes affects m^6 A abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including MYC, SOCS2, ADAM19, and PTEN. In this review, we discuss the specific roles of m^6 A missing space 'writers', 'erasers', and 'readers' in normal physiology and how their altered expression promotes tumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis, prognosis, and the development of novel therapies.Natalia Pinello Stephanie Sun Justin Jong-Leong Wong 2018Cancer Biology & Medicine2018,15,4:15
9Marking RNA:m^6A writers,readers,and functions in Arabidopsis显示文摘N^6-methyladenosine(m^6A)emerges as an important modification in eukaryotic mRNAs.m^6A has first been reported in 1974,and its functional significance in mammalian gene regulation and importance for proper development have been well established.An arsenal of writer,eraser,and reader proteins accomplish deposition,removal,and interpretation of the m^6A mark,resulting in dynamic function.This led to the concept of an epitranscriptome,the compendium of RNA species with chemical modification ofthe nucleobases in the cell,in analogy to the epigenome.While m^6A has long been known to also exist in plant mRNAs,proteins involved in m^6A metabolism have only recently been detected by mutant analysis,homology search,and mRNA interactome capture in the reference plant Arabidopsis thaliana.Dysregulation ofthe m^6A modification causes severe developmental abnormalities of leaves and roots and altered timing of reproductive development.Furthermore,m^6A modification affects viral infection.Here,we discuss recent progress in identifying m^6A sites transcriptome-wide,in identifying the molecular players involved in writing,removing,and reading the mark,and in assigning functions to this RNA modification in 4.thaliana.We highlight similarities and differences to m^6A modification in mammals and provide an outlook on important questions that remain to be addressed.Marlene Reichel Tino Koster Dorothee Staiger 2019Journal of Molecular Cell Biology2019,11,10:13
10m^6 A RNA甲基化修饰异常在肿瘤中的作用显示文摘N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA(messenger RNA,mRNA)含量最多的化学修饰之一。m6A修饰主要由m6A甲基转移酶(methyltransferase)催化,m6A去甲基酶(demethylase)去除,并由m6A结合蛋白(binding protein)识别。它广泛参与调控mRNA剪接、加工、翻译和降解等生命周期的各个阶段,且与肥胖和肿瘤等多种疾病及异常的生理功能相关。近年的研究发现,肿瘤中m6A相关蛋白质(METTL3/14、WTAP、FTO、ALKBH5、YTHDFs)的异常表达,引发m6A甲基化的失调,调控致癌基因和抑癌基因的表达参与肿瘤的发生与发展,并与患者预后不良密切相关。随着RNA免疫沉淀测序技术与高通量测序技术和液相色谱等检测技术的快速发展,有关m6A在肿瘤发生发展中的作用机制研究的进展迅猛,靶向m6A也成为肿瘤临床治疗的新方向。本文重点对m6A RNA甲基化相关因子在癌症发生发展中的作用及机制进行综述,总结m6A RNA甲基化检测技术的最新进展,梳理现有文献报道的脱甲基酶抑制剂大黄酸、甲氯芬那酸2(meclofenamic acid2,MA2)和右旋羟戊二酸(R-2-hydroxyglutarate,R-2HG)等在肿瘤靶向治疗中的运用,为以m6A RNA甲基化为切入点的肿瘤防治研究提供思路与理论参考。韩娟娟 张新安 艾福录 2020中国生物化学与分子生物学报2020,36,4:11
11胰腺癌病因及发病机制研究进展显示文摘胰腺癌是一种恶性程度极高的消化道恶性肿瘤,缺乏早期筛查、诊断以及有效治疗手段,预后极差。本文总结了近年来胰腺癌发生发展相关的环境因素、遗传因素、表观遗传因素,以及胰腺癌与糖尿病和慢性胰腺炎的关系等研究进展,以期加深对胰腺癌发生和演进过程的理解,为其早期诊断和精准治疗提供新的探索方向。赵思涵 郑健 2022中国癌症防治杂志2022,14,3:11
12RNA m6A修饰与肿瘤显示文摘RNA m6A(N6-methyladenosine,m6A)修饰是由m6A甲基转移酶和去甲基化酶所调节的,整个过程是动态可逆的。m6A修饰可以调控基因的表达,在许多生命进程中发挥着重要的作用。近年来,有文章报道m6A修饰通过调节RNA稳定性,微小RNA处理,mRNA剪切和翻译,在人类肿瘤的发生发展中起着重要作用,包括肺癌、肝癌、乳腺癌、子宫内膜癌和急性髓细胞白血病等。本文总结了RNA m6A修饰与肿瘤的关系,以及RNA m6A修饰在不同肿瘤中的生物学功能,对于研究RNA m6A修饰的靶基因及其所调控的肿瘤发生和发展具有重要意义。陈俊文 王侠 王科峰 2020现代肿瘤医学2020,28,18:8
13Structural Insights into N^6-methyladenosine (m^6A) Modification in the Transcriptome显示文摘More than 100 types of chemical modifications in RNA have been well documented.Recently, several modifications, such as N^6-methyladenosine(m^6 A), have been detected in m RNA,opening the window into the realm of epitranscriptomics. The m^6 A modification is the most abundant modification in m RNA and non-coding RNA(nc RNA). At the molecular level, m^6 A affects almost all aspects of m RNA metabolism, including splicing, translation, and stability, as well as micro RNA(mi RNA) maturation, playing essential roles in a range of cellular processes. The m^6 A modification is regulated by three classes of proteins generally referred to as the 'writer'(adenosine methyltransferase), 'eraser'(m^6 A demethylating enzyme), and 'reader'(m^6 A-binding protein). The m^6 A modification is reversibly installed and removed by writers and erasers, respectively.Readers, which are members of the YT521-B homology(YTH) family proteins, selectively bind to RNA and affect its fate in an m^6 A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6 A modification, and provide our insights into the m^6 A-mediated gene regulation.Jinbo Huang Ping Yin 2018Genomics, Proteomics & Bioinformatics2018,16,2:8
14m6A识别蛋白Ythdf1在精子发生中的作用研究显示文摘目的:构建YTH N6甲基腺苷RNA结合蛋白1(YTH N6-methyladenosine RNA binding protein 1,Ythdf1)的基因敲除小鼠,研究其在小鼠精子发生中的作用。方法:利用CRISPR/Cas9敲除技术及原核注射技术构建Ythdf1基因敲除小鼠模型,通过免疫荧光、HE染色对敲除小鼠睾丸及附睾进行形态学分析,通过交配实验进行生殖力测试,研究Ythdf1基因对雄性小鼠精子发生的影响。结果:RT-PCR结果显示,Ythdf1在1~8周龄雄鼠睾丸中均有表达;成功构建Ythdf1基因敲除小鼠;成年敲除小鼠精子发生、附睾及生育力均无异常。结论:在正常饲养情况下,敲除Ythdf1基因对雄性小鼠精子发生无影响。刘媛媛 宋小玲 王仿竹 齐美杰 沈彬 2019南京医科大学学报(自然科学版)2019,39,2:6
15Epigenetic N6-methyladenosine modification of RNA and DNA regulates cancer显示文摘The biological roles of N6 methylation of nucleic acids have been extensively studied.Adenine methylation of RNA is the most prevalent RNA modification and has widespread effects on RNA splicing,translation,localization,and stability.Aberrant dynamic regulation of RNA N6-methyladenosine(m6 A)has been reported in numerous human diseases,including several cancers.In recent years,eukaryotic DNA N6-methyladenosine(6 mA)has also been reported and implicated in cancer progression and tumorigenesis.In this review,we summarize the contributions of N6-methyladenosine modification to cancer biology and pathogenesis in the context of both RNA and DNA.We also highlight the clinical relevance of targeting these modifications as a therapeutic strategy for cancer.Zhixian Liang Reilly LKidwell Haijing Deng Qi Xie 2020Cancer Biology & Medicine2020,17,1:6
16RNA m^6A修饰及在肿瘤中的作用显示文摘6-甲基腺嘌呤(N6-methyladenosine,m^6A)是真核生物RNA内部序列中最常见的一种修饰方式,该过程依赖于书写器、擦除器、阅读器等三类分子的精准调控。m^6A修饰参与调控基因表达,与肿瘤、神经系统疾病、胚胎发育迟缓等多种疾病相关,近年来该领域成为表观转录组学中新的研究热点。文章详细阐述了m^6A修饰在肿瘤发生发展中的作用,包括m^6A修饰参与肿瘤干细胞自我更新与分化,调控肿瘤细胞增殖以及参与放化疗抵抗,讨论靶向m^6A治疗可能带来的临床干预措施,以期为肿瘤精准治疗提供新手段。孙洁 杨振坤 陆培华 吴兵 2020南京医科大学学报(自然科学版)2020,40,3:5
17m6A识别蛋白Ythdf3在精子发生中的作用研究显示文摘目的:通过基因敲除模型研究N6-甲基腺嘌呤(m6A)识别蛋白Ythdf3在小鼠精子发生过程的调控作用。方法:利用CRISPR/Cas9技术构建Ythdf3基因敲除小鼠,通过免疫荧光和HE染色对敲除小鼠进行表型分析,研究Ythdf3在调控小鼠精子发生过程中的作用。结果:免疫组化染色显示Ythdf3在精原及各级生精细胞核中均有表达;成功构建Ythdf3基因敲除小鼠模型;HE染色显示Ythdf3敲除小鼠睾丸各级生精时相及附睾尾精子与对照相比无明显异常。结论:在正常生理条件下,敲除Ythdf3不影响雄性小鼠精子发生。宋小玲 刘媛媛 王仿竹 沈彬 2019南京医科大学学报(自然科学版)2019,39,6:5
18m6A甲基化在肿瘤中的作用研究进展显示文摘N6-甲基腺苷甲基化(m6A)是mRNA中最常见的修饰形式,m6A在不改变碱基序列的条件下调控基因的转录后水平,因此认为m6A与RNA的代谢过程密切相关。m6A修饰主要与三种类型的蛋白酶相关,编码基因分别为“写入基因”、“擦出基因”和“读取基因”。目前研究表明,m6A与癌症的发生发展密切相关。文章主要就国内外研究进展对m6A修饰的概念,特别是与癌症发生之间的作用进行综述。地里呼玛尔·吐鲁洪 曾慧娟 王少华 2019东南国防医药2019,21,4:5
19m6A RNA甲基化在肿瘤中的研究进展显示文摘RNA甲基化是表观遗传转录组学的重要研究领域。N6-甲基腺嘌呤(N6-methyladenosine,m6A)是mRNA上最丰富的内部修饰,受到甲基转移酶、去甲基化酶动态可逆的调控,并且通过与m6A读取蛋白的结合影响mRNA的加工和代谢过程,调控基因表达。m6A RNA甲基化修饰的异常与肿瘤的发生发展密切相关,但不同肿瘤中的m6A介导的分子机制和作用尚未完全阐明。随着高通量测序与生物信息学的发展,已有多种方法可对m6A甲基化位点进行检测分析。以m6A修饰蛋白作为临床诊治靶标具有潜在的应用价值,特异性调节剂的开发有望为肿瘤治疗提供新的选择。裴雨晴 崔巍 2020中华医学杂志2020,100,7:5
20Reversible N6-methyladenosine of RNA:The regulatory mechanisms on gene expression and implications in physiology and pathology显示文摘N6-methyladenosine(m6A)is the most abundant inner RNA modification in eukaryotes.Due to the development of RNA sequencing technology,the distribution pattern of m6A in the transcriptome has been uncovered.Dynamically,the reversible N6-methylation is mediated by two types of proteins,which are classified as“writers”and“erasers”.Under the association of specific co-factors,writers show spatiotemporal N6-methyltransferase activity.Mechanically,m6A can be recognized by“reader”proteins or can directly modify RNA conformation,and it widely affects gene expression by mediating RNA stability,translation,splicing and export.m6A is involved in a series of physiology processes.Dysregulation of m6A is gradually defined as the pathogenesis of some diseases,e.g.,cancer and cardiovascular disease.Therefore,a good understanding of m6A is essential for molecular biology and pathology research.In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators.The discovered biological and pathological processes affected by m6A are also summarized.We hope that readers with related research interests benefit from our review.Xinyu Fang Mengyang Li Tao Yu Gaoli Liu Jianxun Wang 2020Genes & Diseases2020,7,4:4
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