A comprehensive analysis of differential RNA m6A methylation modifications across the entire transcriptome in PTSD through high-throughput MeRIP sequencing

In recent years, the increasing frequency of traumatic events has drawn greater attention to post-traumatic stress disorder (PTSD). However, its underlying biological mechanisms remain poorly understood. N6-methyladenosine (m6A) methylation is among the most common RNA modifications, yet to our knowledge, no studies to date have reported alterations in m6A methylation in PTSD. We enrolled 27 individuals with PTSD and 32 healthy controls. Quantitative real-time PCR (qRT-PCR) was used to examine expression differences of m6A methyltransferases. MeRIP-seq and RNA-seq were employed to investigate m6A methylation modifications and differentially expressed genes between PTSD patients and controls, followed by bioinformatic analysis. Our findings revealed decreased expression of METTL3 and FTO in peripheral blood mononuclear cells of PTSD patients, along with reduced global m6A methylation levels. MeRIP-seq analysis identified 1243 differentially expressed m6A peaks between groups. These peaks were annotated to 1054 differentially m6A-methylated genes, among which 183 exhibited hypermethylation and 871 showed hypomethylation in the PTSD group. RNA-seq analysis detected 662 differentially expressed genes, including 449 up-regulated and 213 down-regulated genes. In the differentially expressed lncRNA profile, 818 genes were identified, comprising 562 up-regulated and 256 down-regulated genes. GO and KEGG analyses indicated that the differentially methylated genes, mRNAs, and lncRNAs were primarily associated with inflammatory response, myelination alterations, and autonomic nervous system activation. In summary, m6A modification plays a critical role in the development and progression of PTSD. This study provides new insights into the biological mechanisms underlying the disorder.