Comparative Analysis of Human Genes Frequently and Occasionally Regulated by m⁶A Modification

The m⁶A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m⁶A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m⁶A modification (m⁶Afreq genes) and those occasionally regulated by m⁶A modification (m⁶Aocca genes). Compared to the m⁶Aocca genes, the m⁶Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m⁶Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m⁶Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m⁶A epitranscriptomic regulation and other gene expression regulatory machineries.