Centre for Anatomy & Cell Biology, Division of Cell-and Developmental Biology, Medical University of Vienna, Schwarzspanierstrasse 17, Haus C, 1st Floor, 1090 Vienna, Austria.
Genes (Basel). 2021 Feb 26;12(3):345. doi: 10.3390/genes12030345.
RNA modifications, long considered to be molecular curiosities embellishing just abundant and non-coding RNAs, have now moved into the focus of both academic and applied research. Dedicated research efforts (epitranscriptomics) aim at deciphering the underlying principles by determining RNA modification landscapes and investigating the molecular mechanisms that establish, interpret and modulate the information potential of RNA beyond the combination of four canonical nucleotides. This has resulted in mapping various epitranscriptomes at high resolution and in cataloguing the effects caused by aberrant RNA modification circuitry. While the scope of the obtained insights has been complex and exciting, most of current epitranscriptomics appears to be stuck in the process of producing data, with very few efforts to disentangle cause from consequence when studying a specific RNA modification system. This article discusses various knowledge gaps in this field with the aim to raise one specific question: how are the enzymes regulated that dynamically install and modify RNA modifications? Furthermore, various technologies will be highlighted whose development and use might allow identifying specific and context-dependent regulators of epitranscriptomic mechanisms. Given the complexity of individual epitranscriptomes, determining their regulatory principles will become crucially important, especially when aiming at modifying specific aspects of an epitranscriptome both for experimental and, potentially, therapeutic purposes.
RNA 修饰，长期以来被认为是丰富的非编码 RNA 上的分子修饰，现在已经成为学术和应用研究的焦点。专门的研究努力（表观转录组学）旨在通过确定 RNA 修饰图谱和研究建立、解释和调节 RNA 信息潜力的分子机制来阐明其基本原理，这些机制超越了四个经典核苷酸的组合。这导致了在高分辨率下对各种表观转录组进行了映射，并对 RNA 修饰电路异常引起的影响进行了编目。虽然获得的见解范围复杂且令人兴奋，但目前大多数表观转录组学似乎都停留在产生数据的过程中，在研究特定的 RNA 修饰系统时，很少有努力将原因与结果区分开来。本文讨论了该领域的各种知识空白，旨在提出一个具体问题：动态安装和修饰 RNA 修饰的酶是如何被调控的？此外，还将突出各种技术，其发展和使用可能允许识别表观转录组机制的特定和上下文相关的调节剂。鉴于单个表观转录组的复杂性，确定其调控原则将变得至关重要，特别是当旨在修饰表观转录组的特定方面时，无论是出于实验目的还是潜在的治疗目的。
