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| 1 | YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA显示文摘 | Hailing Shi Xiao Wang Zhike Lu Boxuan S Zhao Honghui Ma Phillip J HSU Chang Liu Chuan He | 2017 | Cell Research2017，27，3： | 156 |
| 2 | Ythdc2 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 | 2017 | Cell Research2017，27，9： | 96 |
| 3 | YTH Domain: A Family of N^6-methyladenosine (m^6A) Readers显示文摘Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N^6-methyladenosine(m^6 A)is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to m RNAs, t RNAs, r RNAs, and long non-coding RNAs(lnc RNAs). In mammalian cells, m^6 A can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the m^6 A modification is reversible and dynamic. Moreover, m^6 A is recognized by the YT521-B homology(YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6 A recognition by YTH domaincontaining proteins, which would shed new light on m^6 A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications. | Shanhui Liao Hongbin Sun Chao Xu | 2018 | Genomics, Proteomics & Bioinformatics2018，16，2： | 29 |
| 4 | RNA表观遗传修饰:N^6-甲基腺嘌呤显示文摘N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA(Messenger RNA,m RNA)上含量最多的化学修饰之一。类似于DNA和组蛋白化学修饰,m6A修饰也同样是动态可逆的,可在时间和空间上被甲基转移酶和去甲基酶调控。哺乳动物体内m6A甲基转移酶复合物中有一部分成分已被解析,主要有METTL3(Methyltransferase-like protein 3)、METTL14(Methyltransferase-like protein 14)和WTAP(Wilms tumor 1-associating protein)。m6A去甲基酶肥胖蛋白FTO(Fat mass and obesity associated protein)和ALKBH5(Alk B homolog 5)依赖α-酮戊二酸(α-Ketoglutaric acid,α-KG)和Fe(Ⅱ)对m6A进行氧化去甲基化反应。m6A在生物体内由m6A结合蛋白识别,并介导其行使功能。目前发现的m6A结合蛋白有YTH结构域蛋白YTHDF1(YTH domain-containing family protein 1)、YTHDF2(YTH domain-containing family protein 2)、YTHDC1(YTH domain-containing protein1)和核内HNRNPA2B1(Heterogeneous nuclear ribonucleoproteins A2B1)。本文综述了m6A的分布和相关蛋白介导的m6A功能研究,以期全面理解m6A这一RNA表观遗传新修饰在生命进程中的重要调控作用。 | 张笑 贾桂芳 | 2016 | 遗传2016，38，4： | 19 |
| 5 | Aberrant 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 | 2018 | Cancer Biology & Medicine2018，15，4： | 15 |
| 6 | Marking 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 | 2019 | Journal of Molecular Cell Biology2019，11，10： | 13 |
| 7 | CPSF30-L-mediated recognition of mRNA m^(6)A modification controls alternative polyadenylation of nitrate signaling-related gene transcripts in Arabidopsis显示文摘N6-methyladenosine(m^(6)A),a ubiquitous internal modification of eukaryotic mRNAs,plays a vital role in almost every aspect of mRNA metabolism.However,there is little evidence documenting the role of m^(6)A in regulating alternative polyadenylation(APA)in plants.APA is controlled by a large protein-RNA complex with many components,including CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30(CPSF30).In Arabidopsis,CPSF30 has two isoforms and the longer isoform(CPSF30-L)contains a YT512-B Homology(YTH)domain,which is unique to plants.In this study,we showed that CPSF30-L YTH domain binds to m^(6)A in v itro.In the cpsf30-2 mutant,the transcripts of many genes including several important nitrate signaling-related genes had shifts in polyadenylation sites that were correlated with m^(6)A peaks,indicating that these gene transcripts carrying m^(6)A tend to be regulated by APA.Wild-type CPSF30-L could rescue the defects in APA and nitrate metabolism in cpsf30-2,but m^(6)A-binding-defective mutants of CPSF30-L could not.Taken together,our results demonstrated that m^(6)A modification regulates APA in Arabidops is and revealed that the m^(6)A reader CPSF30-L affects nitrate signaling by controlling APA,shedding new light on the roles of the m^(6)A modification during RNA 3-end processing in nitrate metabolism. | Yiteng Hou Jing Sun Baixing Wu Yangyang Gao Hongbo Nie Zhentian Nie Shuxuan Quan Yong Wang Xiaofeng Cao Sisi Li | 2021 | Molecular Plant2021，14，4： | 12 |
| 8 | Structural 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 | 2018 | Genomics, Proteomics & Bioinformatics2018，16，2： | 8 |
| 9 | The m6A methylation regulates gonadal sex differentiation in chicken embryo显示文摘Background:As a ubiquitous reversible epigenetic RNA modification,N6-methyladenosine(m6A)plays crucial regulatory roles in multiple biological pathways.However,its functional mechanisms in sex determination and differentiation during gonadal development of chicken embryos are not clear.Therefore,we established a transcriptome-wide m6A map in the female and male chicken left gonads of embryonic day 7(E7)by methylated RNA immunoprecipitation sequencing(MeRIP-seq)to offer insight into the landscape of m6A methylation and investigate the post-transcriptional modification underlying gonadal differentiation.Results:The chicken embryonic gonadal transcriptome was extensively methylated.We found 15,191 and 16,111 m6A peaks in the female and male left gonads,respectively,which were mainly enriched in the coding sequence(CDS)and stop codon.Among these m6A peaks,we identified that 1013 and 751 were hypermethylated in females and males,respectively.These differential peaks covered 281 and 327 genes,such as BMP2,SMAD2,SOX9 and CYP19A1,which were primarily associated with development,morphogenesis and sex differentiation by functional enrichment.Further analysis revealed that the m6A methylation level was positively correlated with gene expression abundance.Furthermore,we found that YTHDC2 could regulate the expression of sex-related genes,especially HEMGN and SOX9,in male mesonephros/gonad mingle cells,which was verified by in vitro experiments,suggesting a regulatory role of m6A methylation in chicken gonad differentiation.Conclusions:This work provided a comprehensive m6A methylation profile of chicken embryonic gonads and revealed YTHDC2 as a key regulator responsible for sex differentiation.Our results contribute to a better understanding of epigenetic factors involved in chicken sex determination and differentiation and to promoting the future development of sex manipulation in poultry industry. | Jianbo Li Xiuan Zhang Xiqiong Wang Congjiao Sun Jiangxia Zheng Junying Li Guoqiang Yi Ning Yang | 2022 | Journal of Animal Science and Biotechnology2022，13，6： | 4 |
| 10 | mRNA m6A甲基化修饰异常与疾病的研究进展显示文摘在RNA中有100多种不同的修饰方式,其中信使RNA(messenger RNA,mRNA)中的N6-甲基腺苷(m6A)修饰是最常见的一种。m6A修饰是一种动态可逆的调节方式,在甲基转移酶复合物(m6A Writers)的酶促反应下发生甲基化,识别并结合于特异的RNA结合蛋白(m6AReaders),通过去甲基酶(m6A Erasers)恢复腺苷,以此实现对转录物的调控。本文分析了mRNA m6A修饰位点的分布以及不同修饰过程中不同组分的功能,重点介绍了m6A的错误修饰与疾病发生间的关系。未来的研究工作还需要更先进的手段去完善关于mRNA m6A修饰位点的测序鉴定,以及对发生m6A修饰的mRNA的定量鉴定,并阐述mRNA m6A修饰异常导致疾病发生的具体机制。 | 张翔 杜娟 陈雅慧 张洁 吴博 殷松娜 | 2019 | 生命的化学2019，39，2： | 3 |
| 11 | YTHDF1 promotes NLRP3 translation to induce intestinal epithelial cell inflammatory injury during endotoxic shock显示文摘Dear editor,Endotoxic shock usually results from infection-induced physiologic, pathologic, and biologic abnormalities(Singer et al., 2016). Undeniably, it is still a profoundly damaging and life-threatening condition for many individuals(Guan et al., 2019;Ding et al., 2021). Studies have shown that it is associated with the accumulation of apoptotic markers(Kayagaki et al., 2015;Zong et al., 2019). | Xin Zong Xiao Xiao Fu Jie Yuanzhi Cheng Mingliang Jin Yulong Yin Yizhen Wang | 2021 | Science China(Life Sciences)2021，64，11： | 3 |
| 12 | RNA m^(6)A修饰与心血管疾病研究进展显示文摘心血管疾病已成为我国成年人群的首位死亡原因。但其病因多样,发生机制至今仍未完全阐明。大量研究表明表观遗传修饰在心血管疾病发生发展中起重要作用。N^(6)-甲基腺苷(m^(6))修饰是RNA最普遍的一种表观遗传修饰。研究提示m^(6)修饰可能在心血管疾病中发挥重要功能。本文就RNA m^(6)修饰在心血管疾病中的调控作用的相关研究进行综述。 | 宁小彤 任晓晓 王来元 陈恕凤 | 2021 | 中国分子心脏病学杂志2021，21，1： | 1 |
| 13 | MRNA N6-甲基腺苷(m6A)修饰与发育调控显示文摘有关RNA的修饰有超过100种不同的修饰方式,其中信使RNA修饰中的N6-甲基腺苷(m6A)是最重要的修饰之一,其由甲基转移酶复合物m6A 'writer'生成,与RNA结合蛋白m6A 'readers'特异性结合,通过去甲基酶m6A'erasers'除去。m6A修饰涉及参与mRNA加工过程中的多个步骤,以此实现其对基因的转录后表达的调节,尤其是能够在发育过渡期间通过靶向m6A标记来降解该转录物,从而调节发育过程。本文重点介绍m6A修饰在发育过程的主要生物学功能及其机制,并比较其在不同物种之间的差异。 | 张翔 陈雅慧 杜娟 张洁 殷松娜 | 2018 | 中国组织化学与细胞化学杂志2018，27，6： | 1 |
| 14 | 猪YTHDF2蛋白原核表达及多克隆抗体的制备显示文摘YTH家族蛋白2(YTH domain-containing family protein,YTHDF2)作为一种m^6A修饰的结合蛋白,可对底物mRNA的剪接,翻译,降解等过程进行调控。本研究通过RT-PCR首次获得了猪YTHDF2编码基因序列,全长1 743 bp,编码580个氨基酸,基因进化树分析显示该基因在各物种间保守性较高。将猪YTHDF2编码基因克隆至原核表达载体pET-28a (+)中,重组质粒pET-28a (+)-YTHDF2在大肠杆菌BL-21菌株中进行原核表达,成功获得了大量带His标签的猪YTHDH2重组蛋白,大小约70 kD。以纯化的重组蛋白为抗原免疫新西兰大白兔制备猪YTHDF2多抗血清,ELISA结果表明制备的兔抗猪YTHDF2多抗血清效价为1:204 800,间接免疫荧光(IFA)和Western blot试验均表明该多克隆抗体具有良好的反应性和特异性。猪YTHDF2基因序列的获得及多克隆抗体的制备为进一步研究YTHDF2在猪mRNA m^6A甲基化过程中的生物学功能奠定了基础。 | 黄童 杜柳阳 张宇 顾金燕 周继勇 | 2019 | 畜牧与兽医2019，51，8： | 1 |
| 15 | N^6-甲基腺嘌呤修饰在临床恶性肿瘤中的研究进展显示文摘N^6-甲基腺嘌呤(m^6A)是发生于哺乳动物mRNA中最为常见的修饰方式,参与mRNA的剪切、翻译和降解,影响基因的表达。近年来,m^6A修饰及其调控蛋白在肿瘤发生发展中的作用已成为生物医学研究的热点领域之一。现从人体器官系统角度,对m^6A修饰及其调控蛋白在多种肿瘤进程中的作用以及分子机制进行综述。 | 黄景涛 刘松梅 | 2019 | 生命科学2019，31，2： | 1 |
| 16 | m^(6)A阅读者YTH蛋白的研究进展显示文摘甲基化是最为广泛存在的真核生物RNA转录后修饰形式。N6-甲基腺苷(m^(6)A)对真核生物基因转录后调控至关重要,近年来的研究揭示m^(6)A通过招募m^(6)A结合蛋白从而影响包括器官建成、肿瘤形成、节律钟调控及X染色体沉默在内的多种生物学进程。YTH蛋白是目前研究最为深入的m^6A结合蛋白,本文从YTH蛋白的分类、识别m^(6)A的分子机理及其生物学功能3个方面详尽阐述了真核生物中存在的多样化的YTH蛋白如何影响具有m^(6)A修饰的RNA的命运,以及如何调控生物体生长发育。最后,讨论了目前YTH蛋白研究仍有待解决的问题,展望了其在药物研发、作物育种等领域中的应用价值。 | 王晓乐 马荣荣 鲁镇飞 马炜炜 | 2021 | 浙江农业科学2021，62，2： | 1 |
| 17 | 牦牛YTHDF2基因克隆及表达谱分析显示文摘YT521-B homology domains 2(YTHDF2)作为RNA结合蛋白,能够识别N6-甲基腺嘌呤(N6-methyladenosine,m6A)修饰,在哺乳动物生长发育中起着关键作用。为了解牦牛(Bos grunniens)YTHDF2基因在牦牛脂肪沉积中的作用,本研究克隆牦牛脂肪组织中的YTHDF2 CDS区并进行生物信息学分析,利用qPCR技术探究YTHDF2 mRNA的时空表达规律。结果发现,YTHDF2 mRNA CDS区全长1743 bp,共编码580个氨基酸;YTHDF2亲缘关系与野牦牛最近;氨基酸等电点是8.87,不稳定系数(Ⅱ)为50.00,蛋白总平均亲水性为-0.66,YTHDF2蛋白总体表现出较强的亲水性,有1个大小为133 bp的YTH保守结构域,无信号肽和跨膜结构域,共有69个潜在磷酸化位点。YTHDF2蛋白高级结构由无规则卷曲(67.59%)、α-螺旋(15.15%)、延伸链(12.24%)和β-转角(4.66%)相互连接而成。YTHDF2与甲基化修饰相关蛋白相互作用,对RNA特异性结合具有重要作用。qPCR结果显示:在空间维度上,YTHDF2基因在牦牛7个组织中均有表达,背最长肌中表达量最高(P<0.05);时间维度上,18和30月龄2个阶段脂肪组织中的YTHDF2表达差异不显著;进一步研究发现在牦牛前体脂肪细胞分化过程中,YTHDF2表达量呈现上升的趋势,4、8和12 d的表达量显著高于0 d(P<0.05))。研究结果显示,牦牛YTHDF2是1个具有YTH保守结构域的碱性不稳定水溶性蛋白,初步表明YTHDF2在牦牛脂肪沉积过程中发挥着重要的作用。本研究为进一步研究牦牛YTHDF2基因对脂肪沉积调控及其功能提供了参考。 | 马兰花 张永峰 顾亚荣 陈祎玮 阎萍 潘和平 | 2022 | 农业生物技术学报2022，30，8： | 1 |
| 18 | m^6A修饰RNA结合蛋白YTHDF2的克隆、表达及其活性分析显示文摘目的构建YTH结构域m^6A结合蛋白2(YTHDF2)重组表达载体,获得具有结合m^6A修饰RNA活性的YTHDF2重组蛋白。方法以mRNA为模板采用RT-PCR方法扩增YTHDF2基因编码区序列,构建p ET-28aYTHDF2重组表达质粒,在大肠杆菌BL21中诱导表达YTHDF2融合蛋白,利用Ni2+-NTA亲和胶纯化融合蛋白,Ni2+-NTA磁球分析融合蛋白活性。结果与结论成功构建了p ET-28a-YTHDF2重组表达载体,纯化获得了YTHDF2融合蛋白,该融合蛋白具有结合m^6A修饰RNA活性。重组YTHDF2融合蛋白的获得为研究m^6A修饰RNA的生物学功能提供了重要工具分子。 | 苏晨 史祥 付汉江 郑晓飞 | 2018 | 军事医学2018，42，1： | 1 |
| 19 | m^6A甲基化修饰对胶质母细胞瘤恶性进展影响的研究现状显示文摘胶质母细胞瘤是成人最常见、最具侵袭性的原发性脑肿瘤,该肿瘤进展快速,预后差。近年来,分子靶向治疗以其特异性和有效性成为胶质母细胞瘤治疗的研究热点,但对胶质母细胞瘤的分子异质性和发病机制尚不清楚。6-甲基腺嘌呤(m^6A)作为真核生物信使RNA(mRNA)中最丰富的内部修饰,参与了人类多种复杂疾病的发生发展过程,尤其在癌症的发生发展中具有重要作用。有研究结果表明m^6A甲基化调控胶质母细胞瘤干细胞的增殖并且当m^6A甲基化减少时可促进胶质母细胞瘤干细胞的恶性进展,但也有研究表明m^6A甲基化水平降低时可抑制胶质母细胞瘤干细胞的恶性进展。因此就目前研究现状看,m^6A的甲基化和去甲基化可能会影响胶质母细胞瘤恶性进展,也是胶质母细胞瘤目前仍存在争议且相关研究较少的一个方向。发现RNA中m^6A的关键功能可能会为胶质母细胞瘤的治疗提供新的思路。 | 石琦 梁伦 黄玮 余永佳 | 2019 | 蛇志2019，31，4： | 0 |
| 20 | YTHDF2蛋白富集早期胃癌血浆中m6A修饰28S rRNA检测分析显示文摘目的 通过YTHDF2蛋白富集血浆中m6A修饰28S rRNA,分析m6A修饰28S rRNA水平差异在早期胃癌肿瘤标志物筛选中的潜在应用价值。方法 基于YTHDF2蛋白特异性结合m6A修饰RNA的特性,采用结合重组蛋白YTHDF2磁球富集血浆中m6A修饰28S rRNA,通过逆转录实时定量PCR(qRT-PCR)方法分析早期胃癌患者和健康者血浆样本中m6A修饰28S rRNA的水平。结果与结论 YTHDF2重组蛋白可富集m6A修饰28S rRNA,qRTPCR检测表明早期胃癌血浆中m6A修饰28S rRNA的水平高于健康者。该研究结果为筛选获得基于m6A修饰RNA分子的胃癌早期诊断标志物分子提供了基础。 | 陈璐 王沙沙 丁可昕 付汉江 葛常辉 令狐恩强 郑晓飞 | 2022 | 军事医学2022，46，5： | 0 |
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