Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma

Abstract

N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms and is an important posttranscriptional mechanism for regulating genes. In previous research, we found that m6A regulator–mediated RNA methylation modification was involved in asthma; however, the specific modified genes are not clear. In this study, we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma. Here, we performed two high-throughput sequencing methods, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and RNA sequencing (RNA-seq) to identify key genes with m6A modification in asthma. Through difference analysis, we found that 416 methylation peaks were significantly upregulated and 152 methylation peaks were significantly downregulated, and it was mainly distributed in 3′ UTR. Furthermore, compared with the control group, there were 2,505 significantly upregulated genes and 4,715 significantly downregulated genes in the asthma group. Next, through a combined analysis of transcriptome and differential peaks, 14 differentially expressed genes related to RNA methylation modification were screened. Finally, through 87 health controls and 411 asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) program, we verified three m6A-modified key genes (BCL11A, MATK, and CD300A) and found that they were mainly distributed in exons and enriched in 3' UTR. Our findings suggested that intervening in m6A-modified genes may provide a new idea for the treatment of asthma.

N6-methyladenosine-methylomic landscape of lung tissues of mice with chronic obstructive pulmonary disease

“…Meanwhile, the distribution characteristics of the m6A peak were roughly the same in the three groups, and were mainly concentrated in the CDS and 3′-UTR areas. This observation is consistent with the peak distribution trend for peripheral nerve injury, allergic asthma, and rectal cancer reported in mice (28)(29)(30). In summary, these results show that m6A modification plays a role in COPD.…”

RNA modifications in pulmonary diseases

“…180 m 6 A methylation is also implicated in the emergence and evolution of asthma, with the most crucial regulatory factor being the YTHDF3 enriched at exon 3′-UTR, which has an impact on asthma related eosinophils. 181,182 FTO regulates motile ciliogenesis. The deficiency of FTO caused the destabilization of FOXJ1 mRNA, which governs the expression of a critical transcription factor essential for ciliary function, consequently displaying potent asthma-like features.…”

“…m 6 A modifications may be a favorable candidate for ARDS therapy 180 . m 6 A methylation is also implicated in the emergence and evolution of asthma, with the most crucial regulatory factor being the YTHDF3 enriched at exon 3′‐UTR, which has an impact on asthma related eosinophils 181,182 . FTO regulates motile ciliogenesis.…”

RNA Epigenetics in Chronic Lung Diseases

“…Targeting ALKBH5 can be used to treat pulmonary fibrosis [ 131 ]. The m 6 A methylation has also been implicated in the pathogenesis of asthma, and YTHDF3 has an effect on eosinophils for severe asthma, which can guide future immunotherapy strategies [ 132 ]. Increased METTL1 level in IPF patients is associated with poor prognosis.…”