Comprehensive analysis of transcriptome-wide m6A methylome in the lung tissues of mice with acute particulate matter exposure

Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The m⁶A methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the m⁶A methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated m⁶A peaks within 1879 genes and 1278 differentially hypomethylated m⁶A peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four m⁶A-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the m⁶A-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.