RNA修饰N-甲基腺苷及其在人类疾病中的意义。

The RNA Modification N-methyladenosine and Its Implications in Human Disease.

作者信息

Batista Pedro J

机构信息

Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Genomics Proteomics Bioinformatics. 2017 Jun;15(3):154-163. doi: 10.1016/j.gpb.2017.03.002. Epub 2017 May 19.

Abstract

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 N-methyladenosine (mA), 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 mA and its implications in human diseases.

摘要

基因调控受损是许多疾病的核心问题,包括发育性疾病和癌症。此外,控制基因表达的分子途径常常是细胞寄生虫(如病毒)的作用靶点。基因表达通过多种机制进行调控,这些机制相互协调以确保每个基因都能正确、及时地表达。其中许多机制作用于RNA分子从转录到翻译的生命周期。最近,涉及RNA修饰的RNA水平的另一层调控引起了科学界的新关注。发现mRNA和长链非编码RNA中存在的一种修饰——N6-甲基腺苷(m6A)可被RNA去甲基化酶的活性去除,这开创了表观转录组学领域;该领域研究RNA功能如何通过转录后修饰的添加或去除来调控,类似于在DNA和蛋白质水平调控基因表达所采用的策略。RNA转录后修饰的丰度由“书写器”复合物(甲基化酶)和“橡皮擦”(RNA去甲基化酶)蛋白的活性决定。随后,RNA修饰的作用表现为RNA结构的改变和/或修饰后的RNA与RNA结合蛋白或调控RNA之间相互作用的调节。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与人类疾病的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7332/5487527/7c92ff869337/gr1.jpg

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