Direct RNA Sequencing for the Study of Synthesis, Processing, and Degradation of Modified Transcripts
Direct RNA Sequencing for the Study of Synthesis, Processing, and Degradation of Modified Transcripts
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DOI：
10.3389/fgene.2020.00394
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发表时间：
2020-04-28
影响因子：
3.7
通讯作者：
Pelizzola, Mattia
中科院分区：
文献类型：
--
作者：
Furlan, Mattia;Tanaka, Iris;Pelizzola, Mattia
几十年来，人们已经知道转录本可以被标记为数十种不同的修饰。然而，我们才刚刚开始绘制这些标记并了解它们的功能影响。高质量的方法被开发用于分析这些标记中的一些，并且可以精细地研究它们对RNA生命周期的特定阶段的影响的方法是可用的，包括RNA代谢标记。由于这些改进，最丰富的标记，包括N-6-甲基腺苷，正在成为标记RNA命运的重要决定因素。然而，我们仍然缺乏直接研究给定RNA分子的标记集如何塑造其命运的方法。从这个角度来看，我们首先回顾了该领域目前的主要方法。然后，我们提出了一个实验和计算的设置，基于直接RNA测序和数学建模，来破译RNA修饰对单个RNA分子和亚型命运的功能后果。
It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of the RNA life-cycle are available, including RNA metabolic labeling. Thanks to these improvements, the most abundant marks, including N-6-methyladenosine, are emerging as important determinants of the fate of marked RNAs. However, we still lack approaches to directly study how the set of marks for a given RNA molecule shape its fate. In this perspective, we first review current leading approaches in the field. Then, we propose an experimental and computational setup, based on direct RNA sequencing and mathematical modeling, to decipher the functional consequences of RNA modifications on the fate of individual RNA molecules and isoforms.