FTO Protein, Human (His)

The FTO protein functions as an RNA demethylase, mediating oxidative demethylation across various RNA species, including mRNAs, tRNAs, and snRNAs. It plays a crucial role in regulating fat mass, adipogenesis, and energy homeostasis. Specifically, FTO targets the most prevalent internal modification of mRNA, N(6)-methyladenosine (m6A), affecting mRNA expression and stability. Additionally, FTO can demethylate m6A in U6 small nuclear RNA (snRNA) and N(6),2'-O-dimethyladenosine cap (m6A(m)). The demethylation of m6A(m) in the 5'-cap by FTO influences mRNA stability by promoting susceptibility to decapping. Acting as a tRNA demethylase, FTO removes N(1)-methyladenine from various tRNAs. Beyond its role in RNA modification, FTO contributes to the regulation of fat mass, adipogenesis, body weight, and thermogenesis. It also plays a significant role in the regulation of dopaminergic midbrain circuitry and acts as an oncogenic factor in certain acute myeloid leukemias by enhancing the expression of target transcripts such as MYC, CEBPA, ASB2, and RARA through m6A demethylation.