Biochemistry, Cellular and Molecular Biology Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biochemistry and Biophysics, Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry and Biophysics, Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94158, USA.
Neurobiol Dis. 2020 Dec;146:105139. doi: 10.1016/j.nbd.2020.105139. Epub 2020 Oct 13.
The blossoming field of epitranscriptomics has recently garnered attention across many fields by findings that chemical modifications on RNA have immense biological consequences. Methylation of nucleotides in RNA, including N6-methyladenosine (mA), 2-O-dimethyladenosine (mA), N1-methyladenosine (mA), 5-methylcytosine (mC), and isomerization of uracil to pseudouridine (Ψ), have the potential to alter RNA processing events and contribute to developmental processes and different diseases. Though the abundance and roles of some RNA modifications remain contentious, the epitranscriptome is thought to be especially relevant in stem cell biology and neurobiology. In particular, mA occurs at the highest levels in the brain and plays major roles in embryonic stem cell differentiation, brain development, and neurodevelopmental disorders. However, studies in these areas have reported conflicting results on epitranscriptomic regulation of stem cell pluripotency and mechanisms in neural development. In this review we provide an overview of the current understanding of several RNA modifications and disentangle the various findings on epitranscriptomic regulation of stem cell biology and neural development.
新兴的 RNA 转录后修饰组学领域最近在多个领域引起了关注,其研究发现 RNA 上的化学修饰具有巨大的生物学后果。RNA 核苷酸的甲基化,包括 N6-甲基腺苷(m6A)、2-O-二甲基腺苷(m1A)、N1-甲基腺苷(m1A)、5-甲基胞嘧啶(m5C)和尿嘧啶异构化为假尿嘧啶(Ψ),有可能改变 RNA 加工事件,并有助于发育过程和不同疾病。尽管一些 RNA 修饰的丰度和作用仍存在争议,但人们认为 RNA 转录后修饰组在干细胞生物学和神经生物学中尤为重要。特别是 m6A 在大脑中的丰度最高,在胚胎干细胞分化、大脑发育和神经发育障碍中发挥重要作用。然而,在这些领域的研究中,关于 RNA 转录后修饰对干细胞多能性的调控以及在神经发育中的作用机制的研究结果存在矛盾。在这篇综述中,我们概述了目前对几种 RNA 修饰的理解,并梳理了 RNA 转录后修饰对干细胞生物学和神经发育的调控的各种发现。