Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Biochem J. 2019 Apr 26;476(8):1227-1245. doi: 10.1042/BCJ20180445.
Nucleic acid modifications in DNA and RNA ubiquitously exist among all the three kingdoms of life. This trait significantly broadens the genome diversity and works as an important means of gene transcription regulation. Although mammalian systems have limited types of DNA modifications, over 150 different RNA modification types have been identified, with a wide variety of chemical diversities. Most modifications occur on transfer RNA and ribosomal RNA, however many of the modifications also occur on other types of RNA species including mammalian mRNA and small nuclear RNA, where they are essential for many biological roles, including developmental processes and stem cell differentiation. These post-transcriptional modifications are enzymatically installed and removed in a site-specific manner by writer and eraser proteins respectively, while reader proteins can interpret modifications and transduce the signal for downstream functions. Dysregulation of mRNA modifications manifests as disease states, including multiple types of human cancer. In this review, we will introduce the chemical features and biological functions of these modifications in the coding and non-coding RNA species.
核酸修饰在 DNA 和 RNA 中普遍存在于所有三个生命领域。这种特性显著拓宽了基因组的多样性,并作为基因转录调控的重要手段。尽管哺乳动物系统中 DNA 修饰的类型有限,但已经鉴定出超过 150 种不同的 RNA 修饰类型,具有广泛的化学多样性。大多数修饰发生在转移 RNA 和核糖体 RNA 上,但许多修饰也发生在其他类型的 RNA 上,包括哺乳动物 mRNA 和小核 RNA,它们对于许多生物学功能至关重要,包括发育过程和干细胞分化。这些转录后修饰由写入器和擦除器蛋白分别以特定方式进行酶促安装和去除,而读取器蛋白可以解释修饰并传递信号以进行下游功能。mRNA 修饰的失调表现为疾病状态,包括多种人类癌症。在这篇综述中,我们将介绍这些修饰在编码和非编码 RNA 中的化学特征和生物学功能。