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

BACKGROUND: Compared with the well-studied 5-methylcytosine (m(5)C) in DNA, the role and topology of epitranscriptome m(5)C remain insufficiently characterized. RESULTS: Through analyzing transcriptome-wide m(5)C distribution in human and mouse, we show that the m(5)C 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 m(5)C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m(5)C methylation is observed at CpG sites. Further analysis reveals that RNA m(5)C 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. CONCLUSIONS: This study provides an in-depth topological characterization of transcriptome-wide m(5)C modification by associating RNA m(5)C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.