Effect of acute PM_2.5 exposure on PTGS2 and RNA m6A modification

Particulate matter 2.5 (PM_2.5) is a prevalent risk factor in many diseases, but its molecular mechanism remains ambiguous and may be diverse. RNA m⁶A is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Some previous animal exposure studies found that PM_2.5 exposure up-regulated m⁶A RNA methylation in the lung, but there is no research on m⁶A RNA methylation in humans from PM_2.5 exposure now. Here, in the present experiment, we performed a panel study of 65 students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined m⁶A RNA modification profiles of peripheral blood mononuclear cells (PBMCs) from subjects after low and high concentrations of ambient PM_2.5 exposure. We applied a linear mixed-effect (LME) model to investigate the association between PM_2.5 exposure and global m⁶A RNA methylation and PTGS2 level in peripheral blood. We found that increased levels of global m6A RNA methylation and PTGS2 level were associated with higher PM_2.5 exposure. Among the methylated mRNAs, PTGS2 was hyper-methylated after high concentrations of PM_2.5 exposure, which coincided with the increased expression of PTGS2 mRNA. In the present study, we determined that PM_2.5 exposure promoted RNA m6A modification, and PTGS2 in peripheral blood could serve as a novel regulatory factor of inflammation induced by PM_2.5 exposure. Furthermore, RNA m⁶A modification may contribute to the altered expression of PTGS2 induced by PM_2.5 exposure. Our finding provided a new perspective for the prevention and treatment of PM_2.5 exposure-induced adverse health effects.