Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Committee on Immunology, The University of Chicago, Chicago, IL, USA.
EMBO J. 2021 Feb 1;40(3):e105977. doi: 10.15252/embj.2020105977. Epub 2021 Jan 20.
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N -methyladenosine (m A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m A exerts its functions and discuss recent advances that underscore the multifaceted role of m A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m A regulators in disease.
RNA 携带多种化学修饰，这些修饰在基因表达调控中发挥着重要作用。N6-甲基腺苷（m6A）由 METTL3/METTL14 甲基转移酶复合物将 mRNA 上，是最常见的 mRNA 修饰。m6A 甲基化通过影响 mRNA 代谢的众多方面来调节基因表达，包括前体 mRNA 处理、核输出、降解和翻译。m6A 甲基化作为转录后基因表达调控的一种方式的重要性，体现在 m6A 介导的基因调控在许多生理和病理生理过程中发挥着关键作用。在这里，我们综述了 m6A 发挥功能的机制的现有知识，并讨论了最近的进展，这些进展强调了 m6A 在基因表达调控中的多方面作用。我们强调了我们对 m6A 在 mRNA 上沉积的调节以及其对 mRNA 降解和翻译的上下文相关影响的理解的进展、m6A 修饰非编码染色体相关 RNA 种类在调节转录中的作用以及 RNA 去甲基酶 FTO 在各种底物上的活性。我们还讨论了靶向 m6A 调节剂在疾病中的治疗潜力的新出现证据。
