m6A mRNA Methylation in the Mammalian Brain: Distribution, Function and Implications for Brain Functions

RNA is abundantly modified by a range of covalent modifications, collectively termed the epitranscriptome. Of these modifications, N6-methyladenosine (m6A) is the most prevalent internal chemical tag in eukaryotic mRNA. Being cotranscriptionally deposited, it regulates almost all aspects of mRNA’s lifetime including maturation into mRNA, stability, distribution and protein translation. While m6A is likely present in all developing and adult mammalian tissues, here we highlight its distribution and reported functions in the mammalian brain. Additionally, we describe its potential to act as an encoding mechanism for activity- and experience-dependent adaptation and memory-formation. Such alterations may be positive when adjusting to outer challenges or negative when involved in maladaptive processes of the brain such as in the development of psychopathologies.

Consequently, studying this layer of gene expression control in the brain, alongside posttranslational regulation of proteins and epigenetics may inform us as to the molecular mechanisms underlying normal and pathological behaviors. Unfortunately, measuring m6A levels, patterns and especially dynamics still poses a major technological challenge especially in such a complicated organ as the brain.