N6-Methyladenosine in RNA and DNA: An Epitranscriptomic and Epigenetic Player Implicated in Determination of Stem Cell Fate.
N6-Methyladenosine in RNA and DNA: An Epitranscriptomic and Epigenetic Player Implicated in Determination of Stem Cell Fate.
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DOI：
10.1155/2018/3256524
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发表时间：
2018
影响因子：
4.3
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Ji P;Wang X;Xie N;Li Y
大量新出现的证据将碱基修饰与干细胞命运的决定联系在一起，如增殖和分化。在被广泛研究的碱基修饰标记中，5-甲基胞嘧啶(5-MC)及其氧化衍生物(5-羟甲基胞嘧啶(5-HMC)、5-甲酰胞嘧啶(5-FC)和5-羧基胞嘧啶(5-CAC))动态地存在于DNA和RNA中，被认为是参与细胞生物学过程调控的重要表观遗传学标记。近年来，DNA(M6dA)、mRNA(M6A)、tRNA等非编码RNA中的N6-甲基腺苷修饰被定义为真核生物中另一个重要的表观遗传和表观转录标记。M6A基因的修饰已被生化、分子和表型表征，包括阐明其甲基转移酶复合体(m6A编写器)、去甲基酶(m6A擦除器)和直接相互作用蛋白(读取器)，但关于DNA m6dA的信息有限。M6A在表观转录和表观基因组中的水平和景观是由编写器和擦除器根据生命周期中自然编程的生长、发育和繁殖阶段进行微调协调而精确和动态地调节的。此外，在认识干细胞中异常的m6A修饰与癌症和神经退行性疾病等疾病之间的联系方面也取得了进展。这些成就鼓舞着科学家们进一步揭示干细胞发育的表观遗传学机制，并剖析干细胞发育异常导致的多种疾病的发病机制。本文将重点介绍m6A甲基化、DNA和RNA修饰在干细胞调控和密切相关疾病发生中的作用的研究进展。此外，本文还对今后的研究方向进行了展望。
Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.
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YTHDF2 通过直接招募 CCR4-NOT 去腺苷酶复合物来破坏含有 m(6)A 的 RNA 的稳定性。
影响因子：
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