Klungland Arne, Dahl John Arne
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.
Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway.
Curr Opin Genet Dev. 2014 Jun;26:47-52. doi: 10.1016/j.gde.2014.05.006. Epub 2014 Jul 5.
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.
虽然几十年前就已注意到信使核糖核酸（mRNA）中存在6-甲基腺嘌呤（m6A）修饰，但逆转这种修饰的第一种酶直到最近才被鉴定出来。如今我们已知有两种甲基转移酶可在mRNA中引入m6A，即甲基转移酶样蛋白3（METTL3）和甲基转移酶样蛋白14（METTL14），并且已经鉴定出两种可去除m6A的去甲基酶，即脂肪量和肥胖相关蛋白（FTO，也称为ALKBH9）和ALKBH5。m6A的保守作用似乎与减数分裂有关，缺乏ALKBH5的小鼠不育。虽然FTO功能丧失突变会导致隐性致死综合征，但FTO基因内含子中的序列变异与肥胖症和2型糖尿病有关。
