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

Ya-Nan Wang,Hong-Zhong Jin

doi:10.3389/fcell.2020.591629

Abstract

N6-methyladenosine (m6A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m6A 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 m6A peaks and lowest m6A peak density. The greatest differences of m6A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m6A was mainly enriched within the CDSs and 3′UTRs, while hypomethylated m6A 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 m6A, and that transcripts with lower expression were more preferentially modified by m6A. Moreover, upregulation of gene expression was often accompanied by upregulation of m6A methylation, suggesting a regulatory role of m6A in psoriasis vulgaris gene expression.

Highlights

Psoriasis is a chronic, systemic, inflammatory disease, affecting about 2% of the world’s population (Greb et al, 2016)
To obtain the transcriptome-wide m6A map of psoriasis vulgaris, we examined three kinds of skin tissue, namely, involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN), using m6A-targeted antibody coupled with high-throughput sequencing (i.e., MeRIP-Seq)
16,868 m6A peaks were identified from 16,520 genes in PP, 22,144 m6A peaks were identified from 17,665 genes in PN, and 20,408 m6A peaks were identified from 17,358 genes in NN (Figure 1A, Supplementary Figure 2, Supplementary Table 4, and Supplementary Data 1)

Summary

Introduction

Systemic, inflammatory disease, affecting about 2% of the world’s population (Greb et al, 2016). In 2014, the WHO adopted a resolution that defines psoriasis as a chronic, non-communicable, painful, disfiguring, and disabling disease for which there is no cure (World Health Organization, 2014). Extensive epidemiological and molecular analyses m6A Methylation in Psoriasis Vulgaris have provided evidence for the involvement of epigenetics in psoriasis vulgaris (Pollock et al, 2017; Rendon and Schäkel, 2019). Epigenetic mechanisms modify gene expression without changing the sequence of the genome, such as long non-coding RNA (lncRNA) and microRNA (miRNA) silencing, and DNA methylation, but RNA modifications in psoriasis vulgaris have not yet been reported (Rendon and Schäkel, 2019)

Methods

Results

Conclusion