title: Dynamic RNA modifications in disease.
abstract: While the presence of 6-methyladenosine (m6A) modifications in mRNA was noted several decades ago, the first enzyme reversing this modification was identified very recently. Today we know of two methyltransferases introducing m6A in mRNA--METTL3 and METTL14--and two demethylases that remove it have been identified-FTO (ALKBH9) and ALKBH5. The conserved role of m6A seems to relate to meiosis, and mice lacking ALKBH5 are infertile. While loss-of-function mutation in FTO causes a recessive lethal syndrome, sequence variants in introns of the FTO gene are associated with obesity and type 2 diabetes.
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, 0315 Oslo, Norway. Electronic address: arne.klungland@medisin.uio.no.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway.
authors.forename: John Arne
authors.initials: JA
authors.lastname: Dahl
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000071502:AlkB Homolog 5, RNA Demethylase; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C010223:N-methyladenosine; D049308:Dioxygenases; C559920:ALKBH5 protein, human; D000071502:AlkB Homolog 5, RNA Demethylase; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C587355:METTL14 protein, human; D008780:Methyltransferases; C468275:METTL3 protein, human; D000241:Adenosine