The RNA Modification N(6)-methyladenosine and Its Implications in Human Disease.
The RNA Modification N(6)-methyladenosine and Its Implications in Human Disease.
复制标题
DOI：
10.1016/j.gpb.2017.03.002
复制
发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Batista PJ
中科院分区：
文献类型：
--
作者：
Batista PJ
基因调控受损是许多疾病的核心，包括发育性疾病和癌症。此外，控制基因表达的分子途径通常是细胞寄生虫（例如病毒）的目标。基因表达通过多种机制进行控制，这些机制相互协调以确保每个基因的正确和及时表达。其中许多机制针对 RNA 分子从转录到翻译的生命周期。最近，涉及RNA修饰的RNA水平的另一层调控重新引起了科学界的兴趣。 N6-甲基腺苷 (m6A) 是一种存在于 mRNA 和长链非编码 RNA 中的修饰，可以通过 RNA 去甲基酶的活性去除，这一发现开创了表观转录组学领域；研究如何通过添加或去除转录后修饰来调节 RNA 功能，类似于在 DNA 和蛋白质水平上调节基因表达的策略。 RNA 转录后修饰的丰度由写入复合物（甲基化酶）和擦除器（RNA 去甲基化酶）蛋白的活性决定。随后，RNA 修饰的效果随着 RNA 结构的变化和/或修饰的 RNA 与 RNA 结合蛋白或调节 RNA 之间相互作用的调节而显现。这些途径的破坏会损害基因表达和细胞功能。本综述重点关注 RNA 修饰 m6A 及其对人类疾病的影响之间的联系。
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.