Following its transcription, RNA can be modified by >170 chemically distinct types of modifications — the epitranscriptome. In recent years, there have been substantial efforts to uncover and characterize the modifications present on mRNA, motivated by the potential of such modifications to regulate mRNA fate and by discoveries and advances in our understanding of N⁶-methyladenosine (m⁶A). Here, we review our knowledge regarding the detection, distribution, abundance, biogenesis, functions and possible mechanisms of action of six of these modifications — pseudouridine (Ψ), 5-methylcytidine (m⁵C), N¹-methyladenosine (m¹A), N⁴-acetylcytidine (ac⁴C), ribose methylations (N_m) and N⁷-methylguanosine (m⁷G). We discuss the technical and analytical aspects that have led to inconsistent conclusions and controversies regarding the abundance and distribution of some of these modifications. We further highlight shared commonalities and important ways in which these modifications differ with respect to m⁶A, based on which we speculate on their origin and their ability to acquire functions over evolutionary timescales.

在转录之后，RNA 可以通过超过 170 种化学上不同的修饰类型——表观转录组进行修饰。近年来，由于此类修饰具有调节 mRNA 命运的潜力以及我们对N ⁶ -甲基腺苷 (m ⁶ A)理解的发现和进步，人们做出了大量努力来揭示和表征 mRNA 上存在的修饰。在这里，我们回顾了我们关于六种修饰的检测、分布、丰度、生物发生、功能和可能的作用机制的知识——假尿苷 (Ψ)、5-甲基胞苷 (m ⁵ C)、N ¹ -甲基腺苷 (m ¹ A ), N ^{4 -}乙酰胞苷 (ac⁴ C)、核糖甲基化(N _m )和N ^{7 -}甲基鸟苷(m ⁷ G)。我们讨论了导致关于这些修改的丰度和分布的不一致结论和争议的技术和分析方面。我们进一步强调了这些修改在 m ⁶ A方面不同的共同点和重要方式，我们据此推测它们的起源和它们在进化时间尺度上获得功能的能力。