Topological Characterization of Human and Mouse m(5)C Epitranscriptome Revealed by Bisulfite Sequencing.

Topological Characterization of Human and Mouse m(5)C Epitranscriptome Revealed by Bisulfite Sequencing.
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亚硫酸氢盐测序揭示人类和小鼠 m(5)C 表观转录组的拓扑特征

DOI:
10.1155/2018/1351964
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发表时间:
2018
影响因子:
2.9
通讯作者:
Meng J
Meng J
中科院分区:
生物学4区
文献类型:
--
作者:
Wei Z;Panneerdoss S;Timilsina S;Zhu J;Mohammad TA;Lu ZL;de Magalhães JP;Chen Y;Rong R;Huang Y;Rao MK;Meng J

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与 DNA 中经过充分研究的 5-甲基胞嘧啶 (m5C) 相比,表观转录组 m5C 的作用和拓扑结构仍未得到充分表征。 通过分析人类和小鼠转录组范围内的 m5C 分布,我们发现 m5C 修饰在人类和小鼠 mRNA 的 5' 非翻译区 (5'UTR) 处显着富集。通过对 mRNA 和 DNA 甲基化的比较分析,我们证明,与 DNA 甲基化一样,转录组 m5C 甲基化表现出很强的聚类效应。令人惊讶的是,在 CpG 位点观察到 mRNA 和 DNA m5C 甲基化之间呈负相关。进一步分析表明,RNA m5C 甲基化水平与 RNA 表达和 RNA 半衰期呈正相关。我们还观察到线粒体 RNA 的甲基化水平显着高于核基因组转录的 RNA。 这项研究通过将 RNA m5C 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联系起来,提供了转录组范围内 m5C 修饰的深入拓扑表征。
Compared with the well-studied 5-methylcytosine (m5C) in DNA, the role and topology of epitranscriptome m5C remain insufficiently characterized. Through analyzing transcriptome-wide m5C distribution in human and mouse, we show that the m5C 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 m5C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m5C methylation is observed at CpG sites. Further analysis reveals that RNA m5C 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 m5C modification by associating RNA m5C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.
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