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 N⁶-methyladenosine (m⁶A) is the most prevalent modification in eukaryotic mRNAs. This RNA mark is generated by proteins that act as m⁶A writers and can be reversed by proteins that act as m⁶A erasers. The RNA m⁶A modification is also mediated by another group of proteins capable of recognizing m⁶A that act as m⁶A readers. The m⁶A 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, m⁶A 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 m⁶A, 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, m⁶A may play pivotal roles in cytokine and immune response and carcinogenesis.

Keywords: Tumorigenesis; m(6)A erasers; m(6)A modification; m(6)A readers; m(6)A writers.