The Biogenesis and Precise Control of RNA m⁶A Methylation

N⁶-Methyladenosine (m⁶A) is the most prevalent internal RNA modification in mRNA, and has been found to be highly conserved and hard-coded in mammals and other eukaryotic species. The importance of m⁶A for gene expression regulation and cell fate decisions has been well acknowledged in the past few years. However, it was only until recently that the mechanisms underlying the biogenesis and specificity of m⁶A modification in cells were uncovered. We review up-to-date knowledge on the biogenesis of the RNA m⁶A modification, including the cis-regulatory elements and trans-acting factors that determine general de novo m⁶A deposition and modulate cell type-specific m⁶A patterns, and we discuss the biological significance of such regulation.