The m 6 A-independent role of epitranscriptomic factors in cancer.

Protein function alteration and protein mislocalization are cancer hallmarks that drive oncogenesis. N 6 -methyladenosine (m 6 A) deposition mediated by METTL3, METTL16, and METTL5 together with the contribution of additional subunits of the m 6 A system, has shown a dramatic impact on cancer development. However, the cellular localization of m 6 A proteins inside tumor cells has been little studied so far. Interestingly, recent evidence indicates that m 6 A methyltransferases are not always confined to the nucleus, suggesting that epitranscriptomic factors may also have multiple oncogenic roles beyond m 6 A that still represent an unexplored field. To date novel epigenetic drugs targeting m 6 A modifiers, such as METTL3 inhibitors, are entering into clinical trials, therefore, the study of the potential onco-properties of m 6 A effectors beyond m 6 A is required. Here we will provide an overview of methylation-independent functions of the m 6 A players in cancer, describing the molecular mechanisms involved and the future implications for therapeutics.