Methylation of RNA N6-methyladenosine in modulation of cytokine responses and tumorigenesis

Abstract Among myriads of distinct chemical modification in RNAs, the dynamic, reversible and fine-tuned methylation of N 6 -methyladenosine (m 6 A) is the most prevalent modification in eukaryotic mRNAs. This RNA mark is generated by proteins that act as m 6 A writers and can be reversed by proteins that act as m 6 A erasers. The RNA m 6 A modification is also mediated by another group of proteins capable of recognizing m 6 A that act as m 6 A readers. The m 6 A modification exerts direct control over the RNA metabolism including mRNA processing, mRNA exporting, translation initiation, mRNA stability and the biogenesis of long-non-coding RNA (LncRNA), thereby can influence various aspects of cell function. Evidently, m 6 A is intimately associated with cancer development and progression such as self-renewal capacity of cancer stem cells, proliferation, apoptosis and therapeutic resistance, and immune response. In this review, we will discuss the regulation and function of m 6 A, the various functions ascribed to these proteins and the emerging concepts that impact our knowledge of these proteins and their roles in the epitranscriptome. Conceivably, m 6 A may play pivotal roles in cytokine and immune response and carcinogenesis.