RNA demethylases demethylate N6-methyladenosine RNA

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Fe2+- and oxoglutarate-dependent ALKB oxygenase family members are able to oxidatively demethylate alkylated DNA and RNA, thereby repairing them. The family members alpha-ketoglutarate-dependent dioxygenase FTO (FTO) and RNA demethylase ALKBH5 (ALKBH5) localise to the nucleus and can both specifically demethylate N(6)-methyladenosine (m6A) RNA, the most abundant internal modification of messenger RNA (mRNA) in higher eukaryotes (Han et al. 2010, Jia et al. 2011, Xu et al. 2014). FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis and is associated with body mass index (BMI) (Dina et al. 2007, Frayling et al. 2007, Zhang et al. 2015; reviews - Zhao et al. 2014, Merkestein & Sellayah 2015). ALKBH5 could play a role in spermatogenesis. Alkbh5-deficient male mice have increased N6-methyladenosine in mRNA and are characterised by impaired fertility (Zheng et al. 2013).

Literature References
PubMed ID Title Journal Year
24616105 Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition

Liu, Y, Wang, G, Wu, W, Chen, Z, Zhang, Q, Tong, Y, Feng, C, Cheng, C, Deng, Z

J. Biol. Chem. 2014
24627050 FTO and obesity: mechanisms of association

Sun, BF, Zhao, X, Yang, Y, Yang, YG, Zhao, YL

Curr. Diab. Rep. 2014
24778178 Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation

Min, J, Aik, W, Tempel, W, Demetriades, M, Schofield, CJ, Xu, C, Liu, K

J. Biol. Chem. 2014
26788058 Role of FTO in Adipocyte Development and Function: Recent Insights

Sellayah, D, Merkestein, M

Int J Endocrinol 2015
20376003 Crystal structure of the FTO protein reveals basis for its substrate specificity

Niu, T, Wang, Q, Chai, J, Cheng, W, Han, Z, Feng, Y, Wang, J, Zhao, M, Chang, J, Lei, X

Nature 2010
22002720 N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO

Lindahl, T, Zhao, X, Yi, C, Fu, Y, Jia, G, Yang, Y, Dai, Q, He, C, Yang, YG, Pan, T, Zheng, G

Nat. Chem. Biol. 2011
23177736 ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility

Huang, CM, Bogdan, F, Bosmans, RP, Song, SH, Niu, Y, Furu, K, Wang, XJ, Fedorcsak, P, Yang, X, Yang, YG, Tong, WM, Dahl, JA, Krokan, HE, Zhao, WM, Li, CJ, Zhao, X, Fu, Y, Jia, G, He, C, Zheng, G, Liu, J, Lu, Z, Dai, Q, Vågbø, CB, Hao, YJ, Wang, WL, Shi, Y, Klungland, A

Mol. Cell 2013
17434869 A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity

Ring, SM, Walker, M, Wareham, NJ, Perry, JR, Shields, B, McCarthy, MI, Elliott, KS, Cardon, LR, Lawlor, DA, Hitman, GA, Patch, AM, Barrett, JC, Ebrahim, S, Barroso, I, Melzer, D, Bennett, AJ, Ness, AR, Lindgren, CM, Morris, AD, Harries, LW, Ben-Shlomo, Y, Knight, B, Rayner, NW, Palmer, CN, Owen, KR, Karpe, F, Hattersley, AT, Freathy, RM, Groves, CJ, Doney, AS, Ellard, S, Jarvelin, MR, Weedon, MN, Sovio, U, Lango, H, Smith, GD, Ferrucci, L, Frayling, TM, Loos, RJ, Zeggini, E, Timpson, NJ

Science 2007
17496892 Variation in FTO contributes to childhood obesity and severe adult obesity

Le Stunff, C, Balkau, B, Chèvre, JC, Lecoeur, C, Cauchi, S, Vaillant, E, Carlsson, LM, Kovacs, P, Potoczna, N, Hercberg, S, Horber, F, Delplanque, J, Levy-Marchal, C, Froguel, P, Gallina, S, Dina, C, Marre, M, Jacobson, P, Körner, A, Kiess, W, Durand, E, Weill, J, Meyre, D, Bougnères, P, Pattou, F, Ruiz, J, Vatin, V

Nat. Genet. 2007
Catalyst Activity

oxidative RNA demethylase activity of RNA demethylases [nucleoplasm]

Orthologous Events
Cite Us!