Transcriptome-wide assessment of the m6A methylome of intestinal porcine epithelial cells treated with deoxynivalenol

Abstract

Background: Deoxynivalenol (DON) is a cytotoxic compound found in various food and feed products. N6-Methyladenosine (m6A) is a highly abundant epitranscriptomic marker that modifies a wide range of mRNA molecules in mammalian cells. However, the role of the m6A methylome in DON-induced damage remains poorly understood.Results: In this study, we assessed the transcriptome-wide m6A profile of intestinal porcine epithelial cells (IPEC-J2) treated with 1000 ng/mL DON by m6A sequencing and RNA sequencing. Overall, 5406 new m6A peaks appeared with the disappearance of 2615 peaks in DON-treated IPEC-J2 cells. Genes that were uniquely m6A-modified following DON treatment were found to be associated with the tumor necrosis factor (TNF) signaling pathway. On comparing DON-treated and control cells, we identified 733 differentially expressed mRNAs bearing hyper- or hypomethylated m6A peaks. Further experimental data suggested that METTL3-dependent m6A methylation might also play a role in DON-induced inflammatory response, and CSF2 marker is key functional relevance in the context of DON-induced toxicity. Conclusions: This is the first study to perform a transcriptome-wide assessment of the m6A methylome of IPEC-J2 cells treated with DON. We believe that our findings should be useful for identifying mechanisms whereby m6A modifications influence the outcomes of DON exposure.