N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

Abstract

Allergic asthma is well known as a common respiratory disorder comprising an allergic inflammatory nature and excessive immune characteristic. N6-methyladenosine (m6A) methylation is an RNA epigenetic modification that post-transcriptionally regulates gene expression and function by affecting the RNA fate. Currently, m6A methylation is gaining attention as a mechanism of immunoregulation. However, whether m6A methylation engages the pathological process of asthma remains uncertain. Here, we present the m6A methylomic landscape in the lung tissues of ovalbumin-induced acute asthma mice using MeRIP-seq and RNA-seq. We identified 353 hypermethylated m6A peaks within 329 messenger RNAs (mRNAs) and 150 hypomethylated m6A peaks within 143 mRNAs in the lung tissues of asthmatic mice. These differentially methylated mRNAs were found to be involved in several immune function-relevant signaling pathways. In addition, we predicted 25 RNA-binding proteins that recognize the differentially methylated peak sites by exploring public databases, and the roles of these proteins are mostly related to mRNA biogenesis and metabolism. To further investigate the expression levels of the differentially methylated genes, we performed combined analysis of the m6A methylome and transcriptome data and identified 127 hypermethylated mRNAs (107 high and 20 low expression) and 43 hypomethylated mRNAs with differential expressions (9 high and 34 low expression). Of these, there are a list of mRNAs involved in immune function and regulation. The present results highlight the essential role of m6A methylation in the pathogenesis of asthma.

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

“…Accordingly, YT521-B homology (YTH) domain family is the main “readers” ( Jones et al, 2022 ) and “erasers” consisting of FTO and ALKBH5 ( Kaur et al, 2022 ). Recent studies have focused on the importance of m6A modification in tumors ( Jiang et al, 2022 ; Ma et al, 2022 ; Xiong et al, 2022 ; Yadav et al, 2022 ) and non-neoplastic diseases like asthma and pulmonary hypertension ( Teng et al, 2021 ; Zeng et al, 2021 ; Zhou et al, 2021 ). Nevertheless, the expression pattern of m6A regulators in CHP and IPF remains unclear.…”

Cross‐talk of four types of RNA modification writers defines the immune microenvironment in severe asthma

“…Enzymes are proficient catalysts that continuously and efficiently catalyze the production of substrates 26,27 . There is growing evidence that RNA modification plays important roles in asthma progression 28 . Teng et al .…”

“…26,27 There is growing evidence that RNA modification plays important roles in asthma progression. 28 Teng et al found that OVA-induced asthmatic mice had a specific pattern of m 6 A methylation modification compared to healthy mice. 28 Further investigation found that these differentially methylated mRNAs were closely related to immune function, such as inflammatory response, innate immune response, positive regulation of T cell activation, and hematopoietic cell lineage.…”

“…Further investigation found that these differentially methylated mRNAs were closely related to immune function, such as inflammatory response, innate immune response, positive regulation of T cell activation, and hematopoietic cell lineage. Activated WNT signaling pathway positively correlates with airway T H 2 immune responses in asthma patients and is closely related to lung function in asthma patients 28 . Another study on the underlying mechanism of m 6 A modification in the T H 2 immune response in asthma found that OVA‐induced fat mass and obesity‐associated gene ( Fto ) knockout mice exhibited marked motor ciliary defects and an asthma‐like inflammatory phenotype.…”

N6-Methyladenosine Methylomic Landscape of Ureteral Deficiency in Reflux Uropathy and Obstructive Uropathy

“…Throughout life, m 6 A-modified mRNAs play a role in variety of physiological activities, developmental processes and disease pathologies ( 7 , 8 ). Multiple diseases, such as heart failure ( 9 ), type 2 diabetes ( 10 ), kidney injury ( 11 ) and asthma ( 12 ) and various malignancies are associated with changes in m 6 A methylation.…”