Fto Synthesis

FTO belongs to a member of Fe(II)- and α-ketoglutarate-dependent AlkB dioxygenase family and was originally recognized as an enzyme involved in the excision of N1- or N3-modified purine or primidine in both DNA and RNA substrates. Jia et al. for the first time demonstrated that human FTO could also demethylate m6A on nuclear RNAs in vitro, and increase and decrease in m6A was manifested in FTO-depleted and overexpressed-HeLa cell, respectively. FTO function has shown to link to the regulation of body fat homeostasis in human. Consistent with the notion, a study reported that FTO regulates alternative splicing of RUNX1T1, an adipogenic factor, by removing m6As, which are located around splicing junctions. Fto knockout (KO) animal exhibited …show more content…
Although multiple AlkB homologue genes have been identified in mammalian genome, their function and substrates have been elusive. Zheng et al. demonstrated that human ALKBH5 protein efficiently catalyzes demethylation of m6A containing RNAs. Utilization of iron by ALKBH5 protein during catalytic reaction seems to be critical as mutant version (H206A or H266A) of iron center in ALKBH5 protein compromised its demethylation activity. Furthermore, the depletion of ALKBH5 increased the m6A level and accumulated poly[A]-tailed RNA in cytoplasm, causing sterility in male KO …show more content…
As discussed, recent studies highlighted some m6A functions in ESCs and developmental processes. However, there are many remaining questions regarding m6A function in ESC biology. For instances, there are lack of evidences demonstrating definitive functions of both m6A by itself and related enzymes in adult stem cells such as hematopoietic stem cells and intestinal stem cells. In addition, the role of each m6A-modifying enzyme in tissue-specific manner is not investiagted. One way to prove their functions is to use conditional KO strategies as conventional KO of some of enzymes, leading to embryonic lethality. A shift of transcriptome (from maternal transcripts to zygotic transcripts: known as maternal-to-zygotic transition (MZT)) is known to occur during mammalian preimplantation development. A recent study showed that Xenopus oocyte mRNA methylation can regulate translation and cell division during meiosis and early embryo development. Therefore, m6A may possibly play a role in the process of MZT. Finally, the involvement of m6A in onset or progress of human diseases is still elusive. The possibility of this phenomenon in patient derived tissues should be proved in the near future based on experimental