Investigating the structural changes due to adenosine methylation of the Kaposi's sarcoma-associated herpes virus ORF50 transcript.
Investigating the structural changes due to adenosine methylation of the Kaposi's sarcoma-associated herpes virus ORF50 transcript.
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DOI：
10.1371/journal.pcbi.1010150
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发表时间：
2022-05
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
卡波西肉瘤相关疱疹病毒（KSHV）是一种人类癌病毒。KSHV依靠操纵宿主细胞n6 -甲基腺苷（m6A） RNA修饰途径来增强病毒复制。开放阅读框50 （ORF50）的RNA干环内的甲基化通过募集m6A读取器SND1增加转录本的稳定性。在这篇文章中，我们探索了ORF50的未甲基化和甲基化RNA茎环的能量景观，以研究甲基化对茎环结构的影响。我们观察到在茎环顶部的开放和封闭配置之间的甲基化发生了显著的变化。在未甲基化的茎环中，闭合构型的能量要低得多，因此表现出更高的占用率。在这篇文章中，我们提出了在其一个碱基的化学变化的RNA调控分子的结构变化的调查。真核RNA包含100多种不同类型的化学修饰，可以微调RNA的结构和功能。由于RNA系统需要采用特定的3D形状才能发挥功能，因此了解化学修饰如何影响所采用的结构非常重要。利用能量景观探索的计算技术，即探索在给定能量下系统可用的结构，我们能够表征修饰前后的RNA，并了解系统可以采用的结构集合之间的主要区别是什么。在这项工作中，我们介绍了我们对一种致癌病毒编码RNA的研究结果。我们展示了在天然结构的精确位置进行化学修饰如何影响整个系统，诱导远离修饰位点的部分结构的重排。
Kaposi’s sarcoma-associated herpes virus (KSHV) is a human oncovirus. KSHV relies on manipulating the host cell N6-methyl adenosine (m6A) RNA modification pathway to enhance virus replication. Methylation within a RNA stem loop of the open reading frame 50 (ORF50) increases transcript stability via the recruitment of the m6A reader, SND1. In this contribution we explore the energy landscapes of the unmethylated and methylated RNA stem loops of ORF50 to investigate the effect of methylation on the structure of the stem loop. We observe a significant shift upon methylation between an open and closed configuration of the top of the stem loop. In the unmethylated stem loop the closed configuration is much lower in energy, and, as a result, exhibits higher occupancy. In this article we present the investigation of the change in structure of an RNA regulatory molecule upon a change in the chemistry of one of its bases. Eukaryotic RNAs contain more than 100 different types of chemical modifications, which can fine-tune the structure and function of RNA. Since RNA systems need to adopt a specific 3D shape to be functional, it is important to understand how a chemical modification impacts the structure adopted. Using the computational technique of energy landscape explorations, that is exploring what structures are available to the system at a given energy, we are able to characterise the RNA before and after the modification, and understand what the main differences between the ensembles of structures, which can be adopted by the system, are. In this work, we present our results of this investigation on an oncogenic virus-encoded RNA. We show how a chemical modification at a precise location of the native structure affects the system globally, inducing a rearrangement of parts of the structure, which are far away from the modification site.
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影响因子：
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