Figure 5: A proposed model of dynamic regulation of RNA modifications by FTO.
From: FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA
Instead of direct demethylation, a delayed model is proposed for FTO, which possesses different kinetic behaviour to accommodate additional diffusion/export process and avoid direct remethylation. The nascent transcribed RNA is partially methylated by methyltransferase to m6A. m6A is converted to hm6A in regions with low FTO levels, and to f6A in regions with high FTO levels. Demethylated A is produced after the decomposition of hm6A and f6A, which is slower than the diffusion/export process, and which may help to avoid the remethylation by methyltransferase at the nuclear speckles. When RNA is processed and exported to the cytoplasm, different modifications on mRNA can potentially recruit or repel different protein factors, which could affect the metabolisms of mRNA. hm6A and f6A in RNA will eventually be hydrolysed to A; these modifications may also serve as markers for nascent RNA.
