The metabolic baton: conducting the dance of N6-methyladenosine writing and erasing

The modification N6-methyladenosine (m⁶A) plays an important role in determining the functional output of gene expression programs. Throughout the transcriptome, the levels of m⁶A are tightly regulated by the opposing activities of methyltransferases and demethylases, as well as the interaction of modified transcripts with m⁶A-dependent RNA-binding proteins that modulate transcript stability, often referred to as writers, erasers, and readers. The enzymatic activities of both writers and erasers are tightly linked to the cellular metabolic environment, as these enzymatic reactions rely on metabolism intermediaries as cofactors. In this review, we highlight the examples of intersection between metabolism and m⁶A-dependent gene regulation and discuss the different contexts where this interaction plays important roles.