N6-methyl-adenosine (m(6)A) is the most abundant modification in mammalian mRNA and long non-coding RNA. First discovered in the 1970s, m(6)A modification has been proposed to function in mRNA splicing, export, stability, and immune tolerance. Interest and excitement in m(6)A modification has recently been revived based on the discovery of a mammalian enzyme that removes m(6)A and the application of deep sequencing to localize modification sites. The m(6)A demethylase fat mass and obesity associated protein (FTO) controls cellular energy homeostasis and is the first enzyme discovered that reverses an RNA modification. m(6)A Sequencing demonstrates cell-type- and cell-state-dependent m(6)A patterns, indicating that m(6)A modifications are highly regulated. This review describes the current knowledge of mammalian m(6)A modifications and future perspectives on how to push the field forward.
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