A molecular-level perspective on the frequency, distribution, and consequences of messenger RNA modifications.
A molecular-level perspective on the frequency, distribution, and consequences of messenger RNA modifications.
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DOI：
10.1002/wrna.1586
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Koutmou KS
中科院分区：
文献类型：
--
作者：
Jones JD;Monroe J;Koutmou KS
细胞使用化学修饰来改变大生物分子的空间、电荷和构象，调节它们的生物发生、功能和稳定性。直到最近，转录后RNA修饰被认为在很大程度上限于非蛋白质编码RNA种类。然而，随着蛋白质编码信使RNA（mRNA）中大量修饰的发现，这一教条迅速转变。全基因组测序技术的最新进展使mRNA修饰成为基因调控的一个潜在的新前沿，从而导致了表转录组领域的发展。因此，出现了一系列突破性的发现，包括新的修饰、核苷修饰酶（“写入器”和“擦除器”）和识别化学修饰的RNA结合蛋白（“读取器”）。这些发现打开了理解转录后mRNA修饰如何调节mRNA生命周期的大门，并建立了表位转录组与人类健康和疾病之间的联系。尽管越来越多的人认识到它们的重要性，但关于mRNA修饰的身份、流行率和功能后果的基本问题仍有待回答。在这里，我们强调定量研究，表征mRNA修饰丰度，频率和与细胞机制的相互作用。随着该领域的发展，我们认为需要进一步整合定量和还原主义方法来补充全转录组研究，以便建立一个分子水平的框架来理解mRNA化学修饰对生物过程的影响。
Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until recently post-transcriptional RNA modifications were thought to be largely limited to nonprotein coding RNA species. However, this dogma has rapidly transformed with the discovery of a host of modifications in protein coding messenger RNAs (mRNAs). Recent advancements in genome-wide sequencing technologies have enabled the identification of mRNA modifications as a potential new frontier in gene regulation—leading to the development of the epitranscriptome field. As a result, there has been a flurry of multiple groundbreaking discoveries, including new modifications, nucleoside modifying enzymes (“writers” and “erasers”), and RNA binding proteins that recognize chemical modifications (“readers”). These discoveries opened the door to understanding how post-transcriptional mRNA modifications can modulate the mRNA lifecycle, and established a link between the epitranscriptome and human health and disease. Despite a rapidly growing recognition of their importance, fundamental questions regarding the identity, prevalence, and functional consequences of mRNA modifications remain to be answered. Here, we highlight quantitative studies that characterize mRNA modification abundance, frequency, and interactions with cellular machinery. As the field progresses, we see a need for the further integration of quantitative and reductionist approaches to complement transcriptome wide studies in order to establish a molecular-level framework for understanding the consequences of mRNA chemical modifications on biological processes.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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