5-Methylthioadenosine (MTA) is a naturally occurring sulfur-containing nucleoside present in all mammalian tissues. The major source of MTA in cells is formed from S-adenosylmethionine during the synthesis of the polyamines spermine and spermidine. In most cells MTA does not accumulate is significant amounts and is rapidly metabolized by 5-methythioadenosine phosphorylase (MTAP) to yield adenine (Ade) and 5-methylthioribose-1-phosphate (MTR1P). The removal of accumulating MTA by MTAP is necessary for the cell to carry out polyamine metabolism, since MTA is a strong inhibitor of spermine synthase. Intracellular fluctuations in MTA levels could participate in the regulation of the liver proliferative response, and administration of MTA have hepatorptective effect in a model of CCl4-induced chronic liver damage.

N-Methyladenosine (m6A) is a methylated adenine residue and an endogenous urinary nucleoside product of the degradation of transfer ribonucleic acid (tRNA). Adenosine methylation is directed by a large m6A methyltransferase complex containing METTL3 as the SAM-binding sub-unit. In vitro, this methyltransferase complex preferentially methylates RNA oligonucleotides containing GGACU and a similar preference was identified in vivo in mapped m6A sites in Rous sarcoma virus genomic RNA and in bovine prolactin mRNA. More recent studies have characterized other key components of the m6A methyltransferase complex in mammals, including METTL14, Wilms tumor 1 associated protein (WTAP) and KIAA1429. Following a 2010 speculation of m6A in mRNA being dynamic and reversible, the discovery of the first m6A demethylase, fat mass and obesity-associated protein (FTO) in 2011 confirmed this hypothesis and revitalized the interests in the study of m6A. A second m6A demethylase alkB homolog 5 (ALKBH5) was later discovered as well. The biological functions of m6A are mediated through a group of RNA binding proteins that specifically recognize the methylated adenosine on RNA. These binding proteins are named m6A readers. The YT521-B homology (YTH) domain family of proteins (YTHDF1, YTHDF2, YTHDF3, and YTHDC1) have been characterized as direct m6A readers and have a conserved m6A-binding pocket. These m6A readers, together with m6A methyltransferases (writers) and demethylases (erasers), establish a complex mechanism of m6A regulation in which writers and erasers determine the distributions of m6A on RNA, whereas readers mediate m6A-dependent functions. m6A has also been shown to mediate a structural switch termed m6A switch. Considering the versatile functions of m6A in various physiological processes, it is thus not surprising to find links between m6A and numerous human diseases; many originated from mutations or single nucleotide polymorphisms (SNPs) of cognate factors of m6A. The linkages between m6A and numerous cancer types have been indicated in reports that include stomach cancer, prostate cancer, breast cancer, pancreatic cancer, kidney cancer, mesothelioma, sarcoma, and leukemia. The depletion of METTL3 is known to cause apoptosis of cancer cells and reduce the invasiveness of cancer cells, while the activation of ALKBH5 by hypoxia was shown to cause cancer stem cell enrichment. m6A has also been indicated in the regulation of energy homeostasis and obesity, as FTO is a key regulatory gene for energy metabolism and obesity. SNPs of FTO have been shown to associate with body mass index in human populations and occurrence of obesity and diabetes. The influence of FTO on pre-adipocyte differentiation has been suggested. The connection between m6A and neuronal disorders has also been studied. For instance, neurodegenerative diseases may be affected by m6A as the cognate dopamine signaling was shown to be dependent on FTO and correct m6A methylation on key signaling transcripts. The mutations in HNRNPA2B1, a potential reader of m6A, have been known to cause neurodegeneration.