Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Curr Opin Struct Biol. 2021 Aug;69:1-10. doi: 10.1016/j.sbi.2020.12.006. Epub 2021 Jan 11.
RNA undergoes extensive biochemical modification following transcription. In addition to RNA splicing, transcripts are processed by a suite of enzymes that alter the chemical structure of different nucleobases. Broadly termed as 'RNA editing,' these modifications impart significant functional changes to translation, localization, and stability of individual transcripts within the cell. These changes are dynamic and required for a number of critical cellular processes, and dysregulation of these pathways is responsible for several disease states. Accurately detecting, measuring, and mapping different RNA modifications across the transcriptome is vital to understanding their broader functions as well as leveraging these events as diagnostic biomarkers. Here, we review recent advances in profiling several types of RNA modifications, with particular emphasis on adenosine-to-inosine (A-to-I) and N-methyladenosine (mA) RNA editing. We especially highlight approaches that utilize proteins to detect or enrich modified RNA transcripts before sequencing, and we summarize recent insights yielded from these techniques.
RNA 在转录后会经历广泛的生化修饰。除了 RNA 剪接,转录本还会被一系列改变不同核苷酸碱基化学结构的酶进行加工。这些修饰被广泛称为“RNA 编辑”,它们赋予了单个转录本在细胞内翻译、定位和稳定性方面的显著功能变化。这些变化是动态的,是许多关键细胞过程所必需的,而这些途径的失调是几种疾病状态的原因。准确检测、测量和绘制转录组中不同的 RNA 修饰对于理解它们的广泛功能以及利用这些事件作为诊断生物标志物至关重要。在这里,我们回顾了几种 RNA 修饰谱分析的最新进展,特别强调了腺苷到肌苷(A 到 I)和 N6-甲基腺苷(m6A)RNA 编辑。我们特别强调了利用蛋白质在测序前检测或富集修饰 RNA 转录本的方法,并总结了这些技术所带来的最新见解。