mA describes the methylation of the nitrogen at position 6 in the adenosine base within mRNA. Discovered in 1974, mA is the most abundant eukaryotic mRNA modification; most mRNAs contain approximately three mA residues. However, some mRNA transcripts do not contain any mA at all, while others may have 10 or more. The term "epitranscriptome" was coined following transcriptome-wide mappings of mA sites, but does not necessarily exclude other post-transcriptional mRNA modifications. How, and in response to what stimulus, the cell endogenously regulates the level of mA methylation remains unclear at present. However, it is known that the levels of this epitranscriptional mark are dynamically altered during embryonic development. Moreover, environmental stimuli such as stress can also alter the levels of mA.
The mA mRNA methylomes of different eukaryotic organisms have two common characteristics. First of all, the mark is usually found in the R[G > A]mAC[U>A>C>] or RRmACH sequence. Secondly, this mark is enriched in specific regions of the transcriptome; it is mostly found close to stop codons, in 3’-UTRs and in long internal exons. Nevertheless, mA levels vary between different RNAs within a cell and between different cell types of the same organism. The mechanisms controlling the addition of mA to some types of RNA have been described, but others remain unknown.