Mechanistic insights into m⁶A RNA enzymes

The field of RNA modifications, so-called epitranscriptomics, has flourished over the past years owing to improvements of detection methods and the identification of important regulatory players. N6-methyladenosine (m⁶A) is the most abundant internal modification in messenger (mRNA) and long non-coding (lncRNA), and controls most steps of RNA metabolism. Its physiological roles range from gametogenesis, stem cell differentiation to immunity, neuronal development and functions, while its alterations are associated with cancer development and progression. In this review we focus on the proteins that catalyze formation of m⁶A (also called writers) on RNA. Interestingly, distinct proteins deposit m⁶A on different classes of RNA, indicating that specific RNA features dictate recognition mechanisms. Associated factors and post-translational modifications can also alter m⁶A enzyme activity. A better understanding of the underlying regulation involved in m⁶A deposition is the first step towards developing tools for cancer therapy and for treatment of other m⁶A-associated diseases.