Wei Zhen, Panneerdoss Subbarayalu, Timilsina Santosh, Zhu Jingting, Mohammad Tabrez A, Lu Zhi-Liang, de Magalhães João Pedro, Chen Yidong, Rong Rong, Huang Yufei, Rao Manjeet K, Meng Jia
Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China.
Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, L7 8TX Liverpool, UK.
Int J Genomics. 2018 Jun 13;2018:1351964. doi: 10.1155/2018/1351964. eCollection 2018.
Compared with the well-studied 5-methylcytosine (mC) in DNA, the role and topology of epitranscriptome mC remain insufficiently characterized.
Through analyzing transcriptome-wide mC distribution in human and mouse, we show that the mC modification is significantly enriched at 5' untranslated regions (5'UTRs) of mRNA in human and mouse. With a comparative analysis of the mRNA and DNA methylome, we demonstrate that, like DNA methylation, transcriptome mC methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA mC methylation is observed at CpG sites. Further analysis reveals that RNA mC methylation level is positively correlated with both RNA expression and RNA half-life. We also observed that the methylation level of mitochondrial RNAs is significantly higher than RNAs transcribed from the nuclear genome.
This study provides an in-depth topological characterization of transcriptome-wide mC modification by associating RNA mC methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.
与DNA中研究充分的5-甲基胞嘧啶（mC）相比，表观转录组mC的作用和拓扑结构仍未得到充分表征。
通过分析人和小鼠全转录组范围内的mC分布，我们发现mC修饰在人和小鼠mRNA的5'非翻译区（5'UTR）显著富集。通过对mRNA和DNA甲基化组的比较分析，我们证明，与DNA甲基化一样，转录组mC甲基化表现出强烈的聚类效应。令人惊讶的是，在CpG位点观察到mRNA和DNA mC甲基化之间呈负相关。进一步分析表明，RNA mC甲基化水平与RNA表达和RNA半衰期均呈正相关。我们还观察到线粒体RNA的甲基化水平显著高于从核基因组转录的RNA。
本研究通过将RNA mC甲基化模式与转录表达、DNA甲基化、RNA稳定性和线粒体基因组相关联，对全转录组范围的mC修饰进行了深入的拓扑表征。
