RNA modifications have recently emerged as a widespread and complex facet of gene expression regulation. Counting more than 170 distinct chemical modifications with far-reaching implications for RNA fate, they are collectively referred to as the epitranscriptome. These modifications can occur in all RNA species, including messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). In mRNAs, the deposition, removal, and recognition of chemical marks by writers, erasers and readers influence their structure, localization, stability, and translation. In turn, this modulates key molecular and cellular processes such as RNA metabolism, cell cycle, apoptosis, and others. Unsurprisingly, given their relevance for cellular and organismal functions, alterations of epitranscriptomic marks have been observed in a broad range of human diseases, including cancer, neurological and metabolic disorders. Here, we will review the major types of mRNA modifications and editing processes in conjunction with the enzymes involved in their metabolism, and describe their impact on human diseases. We present the current knowledge in an updated catalog. We will also discuss the emerging evidence on the crosstalk of epitranscriptomic marks and what this interplay could imply for the dynamics of mRNA modifications. Understanding how this complex regulatory layer can affect the course of human pathologies will ultimately lead to its exploitation towards novel epitranscriptomic therapeutic strategies.

中文翻译：

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疾病的标志：mRNA 修饰如何塑造遗传和获得性病理

RNA 修饰最近已成为基因表达调控的一个广泛而复杂的方面。计算出 170 多种对 RNA 命运具有深远影响的不同化学修饰，它们统称为表观转录组。这些修饰可以发生在所有 RNA 物种中，包括信使 RNA (mRNA) 和非编码 RNA (ncRNA)。在 mRNA 中，书写者、橡皮擦和阅读器对化学标记的沉积、去除和识别会影响它们的结构、定位、稳定性和翻译。反过来，这会调节关键的分子和细胞过程，例如 RNA 代谢、细胞周期、细胞凋亡等。不出所料，鉴于它们与细胞和生物体功能的相关性，已在广泛的人类疾病中观察到表观转录组标记的改变，包括癌症、神经和代谢紊乱。在这里，我们将结合参与代谢的酶回顾 mRNA 修饰和编辑过程的主要类型，并描述它们对人类疾病的影响。我们在更新的目录中展示了当前的知识。我们还将讨论关于表观转录组标记串扰的新证据，以及这种相互作用对 mRNA 修饰的动力学可能意味着什么。了解这个复杂的调控层如何影响人类病理学的进程将最终导致其开发新的表观转录组学治疗策略。我们在更新的目录中展示了当前的知识。我们还将讨论关于表观转录组标记串扰的新证据，以及这种相互作用对 mRNA 修饰的动力学可能意味着什么。了解这个复杂的调控层如何影响人类病理学的进程将最终导致其开发新的表观转录组学治疗策略。我们在更新的目录中展示了当前的知识。我们还将讨论关于表观转录组标记串扰的新证据，以及这种相互作用对 mRNA 修饰的动力学可能意味着什么。了解这个复杂的调控层如何影响人类病理学的进程将最终导致其开发新的表观转录组学治疗策略。