How Natural Enzymes and Synthetic Ribozymes Generate Methylated Nucleotides in RNA

IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Claudia Höbartner, Katherine E. Bohnsack, Markus T. Bohnsack
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引用次数: 0

Abstract

Methylation of RNA nucleotides represents an important layer of gene expression regulation, and perturbation of the RNA methylome is associated with pathophysiology. In cells, RNA methylations are installed by RNA methyltransferases (RNMTs) that are specialized to catalyze particular types of methylation (ribose or different base positions). Furthermore, RNMTs must specifically recognize their appropriate target RNAs within the RNA-dense cellular environment. Some RNMTs are catalytically active alone and achieve target specificity via recognition of sequence motifs and/or RNA structures. Others function together with protein cofactors that can influence stability, S-adenosyl-L-methionine binding, and RNA affinity as well as aiding specific recruitment and catalytic activity. Association of RNMTs with guide RNAs represents an alternative mechanism to direct site-specific methylation by an RNMT that lacks intrinsic specificity. Recently, ribozyme-catalyzed methylation of RNA has been achieved in vitro, and here, we compare these different strategies for RNA methylation from structural and mechanistic perspectives.
天然酶和合成核糖酶如何在 RNA 中生成甲基化核苷酸
RNA 核苷酸的甲基化是基因表达调控的一个重要层面,RNA 甲基组的干扰与病理生理学有关。在细胞中,RNA 甲基化由专门催化特定类型甲基化(核糖或不同碱基位置)的 RNA 甲基转移酶(RNMTs)完成。此外,RNMTs 还必须在 RNA 密集的细胞环境中特异性地识别适当的目标 RNA。一些 RNMTs 可单独发挥催化作用,并通过识别序列基序和/或 RNA 结构实现目标特异性。其他 RNMTs 则与蛋白质辅助因子一起发挥作用,这些辅助因子可影响稳定性、S-腺苷-L-蛋氨酸结合力和 RNA 亲和力,并有助于特异性招募和催化活性。RNMT 与引导 RNA 的结合是 RNMT 直接进行特定位点甲基化的另一种机制,它缺乏内在的特异性。最近,人们在体外实现了核糖酶催化的 RNA 甲基化,在此,我们从结构和机理的角度对这些不同的 RNA 甲基化策略进行了比较。
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来源期刊
Annual review of biochemistry
Annual review of biochemistry 生物-生化与分子生物学
CiteScore
33.90
自引率
0.00%
发文量
31
期刊介绍: The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.
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