29 m⁶A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

Figure 16

A novel working model was proposed in our study. (1) M⁶A-RMRs differently expressed in acute inflammations, metabolic diseases, autoimmune diseases, organ failures, viral infections, and tumors. (2) Cellular mechanisms such as macrophage polarization, endothelial cell activation, CD4⁺Foxp3⁺ regulatory T cell activation, and resting status, and pathophysiological changes of other cells regulate the transcriptomic changes of m⁶A-RMRs. (3) In folate cycle, transsulfuration pathway, glutathione synthesis, polyamine metabolism, and methionine salvage pathway, homocysteine-methionine cycle serves as a sensor-receptor system to sense the intracellular metabolic homeostasis and stresses of four amino acids such as methionine, homocysteine, serine, and arginine as well as vitamin B12 and folate. The metabolic homeostasis and stress signals relay the metabolic reprogramming signals into cellular methylation processes via various methyltransferases to methylate DNAs, proteins, histones, RNAs, and other molecules. (4) Cell surface receptors such as cytokine receptors, viral receptors, danger-associated molecular pattern (DAMPs) receptors/pathogen-associated molecular pattern (PAMPs) receptors, immune checkpoint receptors, and cosignaling receptors regulate the transcriptomic changes of m⁶A-RMRs. Nuclear transcription factors (TFs) including proinflammatory TFs NF-κB, Jak-STATs, tumor suppressors TP53, PTEN, and APC regulate the transcriptomic changes of m⁶A-RMRs. The figure was created with http://BioRender.com.