Decoding the specificity of m6A RNA methylation and its implication in cancer therapy

N6-methyladenosine (m6A) is the most abundant endogenous modification in eukaryotic RNAs. It plays important roles in various biological processes and diseases, including cancers. More and more studies have revealed that the deposition of m6A is specifically regulated in a context-dependent manner. Here, we review the diverse mechanisms that determine the topology of m6A along RNAs and the cell-type-specific m6A methylomes. The exon junction complex (EJC) as well as histone modifications play important roles in determining the topological distribution of m6A along nascent RNAs, while the transcription factors and RNA-binding proteins, which usually bind specific DNAs and RNAs in a cell-type-specific manner, largely account for the cell-type-specific m6A methylomes. Due to the lack of specificity of m6A writers and readers, there are still challenges to target the core m6A machinery for cancer therapies. Therefore, understanding the mechanisms underlying the specificity of m6A modifications in cancers would be important for future cancer therapies through m6A intervention. [Display omitted] Dr. Jinkai Wang and colleagues summarize diverse mechanisms that specifically regulate m6A. The exon junction complex (EJC) as well as histone modifications play important roles in determining the topological distribution of m6A along nascent RNAs, while the transcription factors and RNA-binding proteins largely account for the cell-type-specific m6A methylomes.