Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
School of Molecular and Cellular Biology and Astbury Centre of Structural Biology, University of Leeds, Leeds, United Kingdom.
PLoS Comput Biol. 2022 May 26;18(5):e1010150. doi: 10.1371/journal.pcbi.1010150. eCollection 2022 May.
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.
卡波西肉瘤相关疱疹病毒（KSHV）是一种人类致癌病毒。KSHV 依赖于操纵宿主细胞 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 茎环内的甲基化通过招募 m6A 阅读器 SND1 增加转录本的稳定性。在本研究中，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闭合构象之间发生了显著的转变。在未甲基化的茎环中，闭合构象的能量更低，因此占据的比例更高。
