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

Background: Compared with the well-studied 5-methylcytosine (m5 C) in DNA, the role and topology of epitranscriptome m5 C remain insufficiently characterized.

Results: Through analyzing transcriptome-wide m5 C distribution in human and mouse, we show that the m5 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 m5 C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m5 C methylation is observed at CpG sites. Further analysis reveals that RNA m5 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 m5 C modification by associating RNA m5 C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.