Abstract

Every type of nucleic acid in cells may undergo some kind of post-replicative or post-transcriptional chemical modification. Recent evidence has highlighted their importance in biology and their chemical complexity. In the following pages, we will describe new discoveries of modifications, with a focus on tRNA and mRNA. We will highlight current challenges and advances in modification detection and we will discuss how changes in nucleotide post-transcriptional modifications may affect cell homeostasis leading to malfunction. Although, RNA modifications prevail in all forms of life, the present review will focus on eukaryotic systems, where the great degree of intracellular compartmentalization provides barriers and filters for the level at which a given RNA is modified and will of course affect its fate and function. Additionally, although we will mention rRNA modification and modifications of the mRNA 5’-CAP structure, this will only be discussed in passing, as many substantive reviews have been written on these subjects. Here we will not spend much time describing all the possible modifications that have been observed; truly a daunting task. For reference, Bujnicki and coworkers have created MODOMICS, a useful repository for all types of modifications and their associated enzymes. Instead we will discuss a few examples, which illustrate our arguments on the connection of modifications, metabolism and ultimately translation. The fact remains, a full understanding of the long reach of nucleic acid modifications in cells requires both a global and targeted study of unprecedented scale, which at the moment may well be limited only by technology.

摘要

细胞中的每种类型的核酸都可能经历某种复制后或转录后的化学修饰。最近的证据强调了它们在生物学中的重要性及其化学复杂性。在接下来的页面中，我们将描述修饰的新发现，重点是 tRNA 和 mRNA。我们将重点介绍当前在修饰检测方面的挑战和进展，我们将讨论核苷酸转录后修饰的变化如何影响导致故障的细胞稳态。尽管 RNA 修饰普遍存在于所有生命形式中，但本综述将重点关注真核系统，其中细胞内的高度分隔为特定 RNA 的修饰水平提供了障碍和过滤器，当然会影响其命运和功能. 此外，虽然我们会提到 rRNA 修饰和 mRNA 5'-CAP 结构的修饰，但这只是顺便讨论，因为已经有许多关于这些主题的实质性评论。在这里，我们不会花太多时间来描述已经观察到的所有可能的修改；确实是一项艰巨的任务。作为参考，Bujnicki 和同事创建了 MODOMICS，这是一个用于所有类型的修饰及其相关酶的有用存储库。相反，我们将讨论一些例子，这些例子说明了我们关于修饰、代谢和最终翻译之间联系的论点。事实仍然如此，要全面了解细胞中核酸修饰的长期影响，需要进行规模空前的全球和有针对性的研究，目前这很可能仅受技术限制。