Transcriptome-Wide mA Methylation in Skin Lesions From Patients With Psoriasis Vulgaris.

N-methyladenosine (mA) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed mA transcriptome-wide profiling in three kinds of skin tissue: involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN). The findings revealed that transcripts of PP contained the fewest mA peaks and lowest mA peak density. The greatest differences of mA methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated mA was mainly enriched within the CDSs and 3'UTRs, while hypomethylated mA was not only enriched within CDSs and 3'UTRs, but also within 5'UTRs. GO and KEGG pathway analyses indicated that hypermethylated transcripts in PP were particularly associated with response-associated terms, cytokine production, and olfactory transduction. Meanwhile, hypomethylated transcripts in PP were mainly associated with development-related processes and the Wnt signaling pathway. In addition, we discovered that 19.3-48.4% of the differentially expressed transcripts in psoriasis vulgaris were modified by mA, and that transcripts with lower expression were more preferentially modified by mA. Moreover, upregulation of gene expression was often accompanied by upregulation of mA methylation, suggesting a regulatory role of mA in psoriasis vulgaris gene expression.