Metabolic Regulation of the Epitranscriptome

Abstract

An emergent theme in cancer biology is that dysregulated energy metabolism may directly influence oncogenic gene expression. This is due to the fact that many enzymes involved in gene regulation use cofactors derived from primary metabolism, including acetyl-CoA, S-adenosylmethionine, and 2-ketoglutarate. While this phenomenon was first studied through the prism of histone and DNA modifications (the epigenome), recent work indicates metabolism can also impact gene regulation by disrupting the balance of RNA post-transcriptional modifications (the epitranscriptome). Here we review recent studies that explore how metabolic regulation of writers and erasers of the epitranscriptome (FTO, TET2, NAT10, MTO1, and METTL16) helps shape gene expression through three distinct mechanisms: cofactor inhibition, cofactor depletion, and writer localization. Our brief survey underscores similarities and differences between the metabolic regulation of the epigenome and epitranscriptome, and highlights fertile ground for future investigation.