Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until recently post-transcriptional RNA modifications were thought to be largely limited to nonprotein coding RNA species. However, this dogma has rapidly transformed with the discovery of a host of modifications in protein coding messenger RNAs (mRNAs). Recent advancements in genome-wide sequencing technologies have enabled the identification of mRNA modifications as a potential new frontier in gene regulation-leading to the development of the epitranscriptome field. As a result, there has been a flurry of multiple groundbreaking discoveries, including new modifications, nucleoside modifying enzymes ("writers" and "erasers"), and RNA binding proteins that recognize chemical modifications ("readers"). These discoveries opened the door to understanding how post-transcriptional mRNA modifications can modulate the mRNA lifecycle, and established a link between the epitranscriptome and human health and disease. Despite a rapidly growing recognition of their importance, fundamental questions regarding the identity, prevalence, and functional consequences of mRNA modifications remain to be answered. Here, we highlight quantitative studies that characterize mRNA modification abundance, frequency, and interactions with cellular machinery. As the field progresses, we see a need for the further integration of quantitative and reductionist approaches to complement transcriptome wide studies in order to establish a molecular-level framework for understanding the consequences of mRNA chemical modifications on biological processes. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Processing > RNA Editing and Modification.

中文翻译：

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关于信使 RNA 修饰的频率、分布和后果的分子水平观点。

细胞使用化学修饰来改变大生物分子的空间、电荷和构象，从而调节它们的生物发生、功能和稳定性。直到最近，转录后 RNA 修饰被认为主要限于非蛋白质编码 RNA 种类。然而，随着蛋白质编码信使 RNA (mRNA) 中大量修饰的发现，这一教条迅速转变。全基因组测序技术的最新进展使 mRNA 修饰成为基因调控的潜在新前沿，从而促进了表观转录组领域的发展。结果，出现了一系列突破性的发现，包括新的修饰、核苷修饰酶（“作家”和“橡皮擦”）、和识别化学修饰的 RNA 结合蛋白（“阅读器”）。这些发现为了解转录后 mRNA 修饰如何调节 mRNA 生命周期打开了大门，并在表观转录组与人类健康和疾病之间建立了联系。尽管人们迅速认识到其重要性，但关于 mRNA 修饰的特性、普遍性和功能后果的基本问题仍有待回答。在这里，我们重点介绍了表征 mRNA 修饰丰度、频率和与细胞机制相互作用的定量研究。随着领域的发展，我们认为需要进一步整合定量和还原方法来补充转录组范围的研究，以便建立一个分子水平的框架来理解 mRNA 化学修饰对生物过程的影响。本文分类如下：RNA 结构和动力学 > RNA 结构、动力学和化学 RNA 加工 > RNA 编辑和修饰。