RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:
22002720, PubMed:
26458103, PubMed:
28002401, PubMed:
30197295, PubMed:
26457839, PubMed:
25452335). Specifically demethylates N(6)- methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:
22002720, PubMed:
26458103, PubMed:
30197295, PubMed:
26457839, PubMed:
25452335). M6A demethylation by FTO affects mRNA expression and stability (PubMed:
30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:
30197295). Mediates demethylation of N(6),2'-O- dimethyladenosine cap (m6A(m)), by demethylating the N(6)- methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:
28002401, PubMed:
30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:
28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:
30197295). Has no activity towards 1-methylguanine (PubMed:
20376003). Has no detectable activity towards double-stranded DNA (PubMed:
20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single- stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3- methylcytosine (PubMed:
18775698, PubMed:
20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:
18775698, PubMed:
20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:
18775698, PubMed:
20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:
26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:
28017614, PubMed:
29249359).
