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

Figure 2

An overview of RNA methylation processes, which include (a) homocysteine-methionine-folate cycles for methyl generation and donation; (b) 29 m⁶A-RNA methylation regulators (m⁶A-RMRs) are classified into five groups: (i) RNA methylation writers, (ii) RNA methylation erasers, (iii) RNA methylation readers, (iv) m⁶A-dependent RNA binding proteins (RBPs), and (v) m⁶A repelled RNAs; (c) the hypothesis we proposed. (a) The methyl group is transferred to proteins, nucleic acids, and other biochemicals from the biochemical reaction of S-adenosylmethione (SAM) to S-adenosylhomocysteine (SAH) in homocysteine-methionine metabolic cycle. For RNA methylation, mRNA, lncRNA, tRNA, SnRNA, pre-miRNA, and CirRNA can be methylated in many different ways. In addition to the basic methylated forms, the common methylated forms include N6-methyladenosine (m⁶A), N1-methyladenosine, N1-methyladenosine, 2-O-methyls at mRNA, N6-methyladenosine at lncRNA, pre-miRNA, circRNA [50–55], N1-methyladenosine at tRNA, 2-O-methyls at rRNA, and snRNA [56]. (b) The reported 29 m⁶A-RMRs were chosen for analysis, including 10 m⁶A methyltransferase enzymes (writers), two m6A demethylases (erasers), 11 m⁶A binding proteins (readers), three m⁶A dependent on RNA binding proteins, and three RNA binding proteins repelled by m⁶A. The detailed information including the reference articles of the 29 m⁶A-RMRs is listed in Supplementary Table 3. (c) The methyl donor is derived from folate cycle and coupled homocysteine-methionine cycle. When the donor source is impaired, the DNA, RNA, and protein methylations will be in disorder. We proposed the hypothesis: mRNA methylation disorders will affect the expressions of m⁶A-RMRs; then, the m⁶A-RMRs will be involved in inflammation, metabolic diseases, and tumors by methylating or demethylating target genes including RNAs.

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