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mA RNA 酶的机制见解。

Mechanistic insights into mA RNA enzymes.

机构信息

Laboratory of RNA Epigenetics, Institute of Molecular Biology (IMB), Mainz 55128, Germany.

Laboratory of RNA Epigenetics, Institute of Molecular Biology (IMB), Mainz 55128, Germany.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2019 Mar;1862(3):222-229. doi: 10.1016/j.bbagrm.2018.10.014. Epub 2018 Nov 3.

Abstract

The field of RNA modifications, so-called epitranscriptomics, has flourished over the past years owing to improvements of detection methods and the identification of important regulatory players. N6-methyladenosine (mA) is the most abundant internal modification in messenger (mRNA) and long non-coding (lncRNA), and controls most steps of RNA metabolism. Its physiological roles range from gametogenesis, stem cell differentiation to immunity, neuronal development and functions, while its alterations are associated with cancer development and progression. In this review we focus on the proteins that catalyze formation of mA (also called writers) on RNA. Interestingly, distinct proteins deposit mA on different classes of RNA, indicating that specific RNA features dictate recognition mechanisms. Associated factors and post-translational modifications can also alter mA enzyme activity. A better understanding of the underlying regulation involved in mA deposition is the first step towards developing tools for cancer therapy and for treatment of other mA-associated diseases.

摘要

RNA 修饰领域,即所谓的表观转录组学,近年来由于检测方法的改进和重要调控因子的鉴定而蓬勃发展。N6-甲基腺苷(m6A)是信使(mRNA)和长非编码(lncRNA)中最丰富的内部修饰,它控制着 RNA 代谢的大多数步骤。其生理作用范围从配子发生、干细胞分化到免疫、神经元发育和功能,而其改变与癌症的发生和发展有关。在这篇综述中,我们重点介绍了催化 RNA 上 m6A 形成的蛋白质(也称为写入器)。有趣的是,不同的蛋白质在不同类别的 RNA 上沉积 m6A,这表明特定的 RNA 特征决定了识别机制。相关因子和翻译后修饰也可以改变 m6A 酶的活性。更好地理解 m6A 沉积所涉及的潜在调控是开发癌症治疗和治疗其他与 m6A 相关疾病的工具的第一步。

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