Landscape and Regulation of m⁶A and m⁶Am Methylome across Human and Mouse Tissues

Area of Science:

• Epitranscriptomics
• RNA modifications
• Gene regulation

Background:

• N⁶-methyladenosine (m⁶A) and N⁶,2"-O-dimethyladenosine (m⁶Am) are key reversible epitranscriptomic marks on mRNA.
• The tissue-specific distribution and regulatory landscape of m⁶A and m⁶Am remain largely uncharacterized.

Purpose of the Study:

• To comprehensively profile the m⁶A and m⁶Am methylomes across diverse human and mouse tissues.
• To investigate the tissue specificity, regulatory mechanisms, and evolutionary conservation of these RNA modifications.

Main Methods:

• Large-scale profiling of m⁶A and m⁶Am modifications in 43 human and 16 mouse tissues.
• Analysis of methylation patterns, correlation with gene expression of modifying enzymes (writers and erasers), and enrichment of single nucleotide polymorphisms (SNPs).
• Cross-species comparative analysis to determine factors influencing methylation patterns.

Main Results:

• Demonstrated significant tissue specificity for m⁶A and m⁶Am, particularly in brain tissues.
• Identified tissue-specific m⁶A peaks capable of classifying tissue types.
• Observed partial correlation between m⁶A/m⁶Am levels and the expression of their associated writer and eraser enzymes.
• Found enrichment of SNPs in m⁶A-modified regions.
• Revealed that species of origin is a stronger determinant of methylation patterns than tissue type.

Conclusions:

• Provided an extensive resource for understanding the landscape and regulation of m⁶A and m⁶Am epitranscriptomic marks in mammals.
• Highlighted the critical role of species in shaping RNA methylation patterns.
• Underscored the potential of m⁶A as a biomarker for tissue classification.