The Regulation Of Body Fat Homeostasis Essay

990 Words Oct 24th, 2016 4 Pages
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 growth retardation with decreased body weight and metabolic anomalies.

ALKBH5, a Fe(II)- and α-ketoglutarate-dependent dioxygenase, is also a member of AlkB family. 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…

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