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N 6 -methyladenosine (m 6 A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m 6 A 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 m 6 A peaks and lowest m 6 A peak density. The greatest differences of m 6 A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m 6 A was mainly enriched within the CDSs and 3′UTRs, while hypomethylated m 6 A 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 m 6 A, and that transcripts with lower expression were more preferentially modified by m 6 A. Moreover, upregulation of gene expression was often accompanied by upregulation of m 6 A methylation, suggesting a regulatory role of m 6 A in psoriasis vulgaris gene expression.

Transcriptome-Wide m6A Methylation in Skin Lesions From Patients With Psoriasis Vulgaris