Institute of Molecular Biology, Academia Sinica, Taipei City 115, Taiwan.
Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
Int J Mol Sci. 2021 Nov 1;22(21):11870. doi: 10.3390/ijms222111870.
The intrinsic cellular heterogeneity and molecular complexity of the mammalian nervous system relies substantially on the dynamic nature and spatiotemporal patterning of gene expression. These features of gene expression are achieved in part through mechanisms involving various epigenetic processes such as DNA methylation, post-translational histone modifications, and non-coding RNA activity, amongst others. In concert, another regulatory layer by which RNA bases and sugar residues are chemically modified enhances neuronal transcriptome complexity. Similar RNA modifications in other systems collectively constitute the cellular epitranscriptome that integrates and impacts various physiological processes. The epitranscriptome is dynamic and is reshaped constantly to regulate vital processes such as development, differentiation and stress responses. Perturbations of the epitranscriptome can lead to various pathogenic conditions, including cancer, cardiovascular abnormalities and neurological diseases. Recent advances in next-generation sequencing technologies have enabled us to identify and locate modified bases/sugars on different RNA species. These RNA modifications modulate the stability, transport and, most importantly, translation of RNA. In this review, we discuss the formation and functions of some frequently observed RNA modifications-including methylations of adenine and cytosine bases, and isomerization of uridine to pseudouridine-at various layers of RNA metabolism, together with their contributions to abnormal physiological conditions that can lead to various neurodevelopmental and neurological disorders.
哺乳动物神经系统的内在细胞异质性和分子复杂性在很大程度上依赖于基因表达的动态性质和时空模式。这些基因表达的特征部分是通过涉及各种表观遗传过程的机制来实现的，如 DNA 甲基化、组蛋白翻译后修饰和非编码 RNA 活性等。此外，另一个调节层通过对 RNA 碱基和糖残基进行化学修饰来增强神经元转录组的复杂性。其他系统中的类似 RNA 修饰共同构成了细胞表转录组，它整合并影响各种生理过程。表转录组是动态的，不断重塑以调节发育、分化和应激反应等重要过程。表转录组的扰动会导致各种病理状况，包括癌症、心血管异常和神经疾病。下一代测序技术的最新进展使我们能够识别和定位不同 RNA 种类上修饰的碱基/糖。这些 RNA 修饰调节 RNA 的稳定性、运输，最重要的是调节 RNA 的翻译。在这篇综述中，我们讨论了在 RNA 代谢的各个层面上形成和功能的一些常见的 RNA 修饰，包括腺嘌呤和胞嘧啶碱基的甲基化，以及尿嘧啶到假尿嘧啶的异构化，以及它们对导致各种神经发育和神经疾病的异常生理状况的贡献。
