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RNA 编辑在表观转录组学和人类健康领域的前沿。

RNA editing in the forefront of epitranscriptomics and human health.

机构信息

Department of Life Sciences, School of Sciences, European University Cyprus, 2404, Nicosia, Cyprus.

Centre for Risk and Decision Sciences (CERIDES), 2404, Nicosia, Cyprus.

出版信息

J Transl Med. 2019 Sep 23;17(1):319. doi: 10.1186/s12967-019-2071-4.

Abstract

Post-transcriptional modifications have been recently expanded with the addition of RNA editing, which is predominantly mediated by adenosine and cytidine deaminases acting on DNA and RNA. Here, we review the full spectrum of physiological processes in which these modifiers are implicated, among different organisms. Adenosine to inosine (A-to-I) editors, members of the ADAR and ADAT protein families are important regulators of alternative splicing and transcriptional control. On the other hand, cytidine to uridine (C-to-U) editors, members of the AID/APOBEC family, are heavily implicated in innate and adaptive immunity with important roles in antibody diversification and antiviral response. Physiologically, these enzymes are present in the nucleus and/or the cytoplasm, where they modify various RNA molecules, including miRNAs, tRNAs apart from mRNAs, whereas DNA editing is also possible by some of them. The expansion of next generation sequencing technologies provided a wealth of data regarding such modifications. RNA editing has been implicated in various disorders including cancer, and neurological diseases of the brain or the central nervous system. It is also related to cancer heterogeneity and the onset of carcinogenesis. Response to treatment can also be affected by the RNA editing status where drug efficacy is significantly compromised. Studying RNA editing events can pave the way to the identification of new disease biomarkers, and provide a more personalised therapy to various diseases.

摘要

RNA 编辑是转录后修饰的最新扩展,主要由作用于 DNA 和 RNA 的腺苷酸和胞苷脱氨酶介导。在这里,我们综述了这些修饰物在不同生物中参与的各种生理过程。腺苷酸到肌苷酸(A-to-I)编辑器,ADAR 和 ADAT 蛋白家族的成员,是可变剪接和转录调控的重要调节剂。另一方面,胞苷到尿苷(C-to-U)编辑器,AID/APOBEC 家族的成员,在先天和适应性免疫中大量涉及,在抗体多样化和抗病毒反应中发挥重要作用。生理上,这些酶存在于细胞核和/或细胞质中,在那里它们修饰各种 RNA 分子,包括 miRNA、tRNA 以及 mRNA,而一些酶也可以进行 DNA 编辑。下一代测序技术的扩展提供了大量关于这些修饰的相关数据。RNA 编辑与包括癌症在内的各种疾病有关,也与大脑或中枢神经系统的神经疾病有关。它还与癌症异质性和致癌发生有关。治疗反应也可能受到 RNA 编辑状态的影响,药物疗效显著降低。研究 RNA 编辑事件可以为识别新的疾病生物标志物铺平道路,并为各种疾病提供更个性化的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa34/6757416/810038b00113/12967_2019_2071_Fig1_HTML.jpg

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