Topological Characterization of Human and Mouse mC Epitranscriptome Revealed by Bisulfite Sequencing.

BACKGROUND

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

RESULTS

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.

CONCLUSIONS

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.