FTO
FTO (FTO alpha-ketoglutarate dependent dioxygenase, also known as fat mass and obesity associated protein, ALKBH9, KIAA1752 and IFEX9) is an RNA demethylase that removes N(6)-methyladenosine from mRNA and other RNA species. It regulates fat mass, adipogenesis and energy homeostasis. Browse Assay Genie's current range of FTO research reagents below, or read on for the biology behind the target.
FTO mediates oxidative demethylation of several RNA species, including mRNAs, tRNAs and snRNAs. Its best-characterised substrate is N(6)-methyladenosine (m6A), the most prevalent internal modification of messenger RNA in higher eukaryotes, and m6A demethylation by FTO affects mRNA expression and stability. FTO also demethylates m6A in U6 small nuclear RNA and the N(6),2'-O-dimethyladenosine cap (m6A(m)) at the second transcribed position of mRNAs and U6 snRNA; removing m6A(m) from the 5'-cap makes transcripts more susceptible to decapping. In tRNAs it removes N(1)-methyladenine. It has no activity towards 1-methylguanine and no detectable activity towards double-stranded DNA.
The FTO protein belongs to the fto family and to the AlkB-related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily, which is grouped by HGNC with the alkylation repair homologs. Related enzymes reverse alkylated DNA and RNA damage by oxidative demethylation, and FTO can demethylate single-stranded RNA containing 3-methyluracil and single-stranded DNA containing 3-methylthymine, with low activity towards 1-methyladenine or 3-methylcytosine in single-stranded DNA. Whether it repairs alkylated nucleic acids in vivo is unsure. UniProt lists the protein in the nucleus, nuclear speckles and cytoplasm.
The FTO gene was originally named for fat mass and obesity association. Studies in mice and humans indicate roles in the nervous and cardiovascular systems and a strong association with body mass index, obesity risk and type 2 diabetes. FTO contributes to the regulation of body size, body fat accumulation and thermogenesis, and to adipocyte differentiation into brown or white fat cells. It also regulates the dopaminergic midbrain circuitry through m6A demethylation of mRNAs. In some acute myeloid leukaemias it acts as an oncogene, demethylating transcripts such as MYC, CEBPA, ASB2 and RARA and promoting their expression.
FTO demethylates m6A and m6A(m) in mRNA and snRNA, making it a central enzyme for studying how RNA methylation affects transcript stability.
FTO regulates fat mass, adipogenesis, thermogenesis and body weight, and the FTO gene is strongly associated with body mass index and obesity risk.
FTO enhances leukaemic oncogene-mediated transformation in acute myeloid leukaemia by demethylating transcripts including MYC, CEBPA, ASB2 and RARA.
FTO regulates dopaminergic midbrain circuitry via m6A demethylation, and has been linked to nervous and cardiovascular systems and type 2 diabetes.
FTO is an RNA demethylase that oxidatively removes methyl groups from RNA, notably m6A in mRNA and U6 snRNA, m6A(m) at the mRNA cap and N(1)-methyladenine in tRNAs. Through this activity it influences mRNA stability and regulates fat mass, adipogenesis and energy homeostasis.
FTO stands for fat mass and obesity associated, and the HGNC name is FTO alpha-ketoglutarate dependent dioxygenase. Aliases and previous symbols include KIAA1752, MGC5149, ALKBH9 and IFEX9. UniProt names the protein alpha-ketoglutarate-dependent dioxygenase FTO.
Mouse and rat both have an ortholog named Fto. Studies in mice and humans link FTO to body mass index, obesity risk and type 2 diabetes, and it has an oncogenic role in some acute myeloid leukaemias. Check the datasheet of any product for its validated reactivity.
Other RNA-modification enzymes, alkylation repair homologs and metabolic and leukaemia-associated targets.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9C0B1; product specifications from Assay Genie datasheets.