Reactome | RNA demethylases demethylate N6-methyladenosine RNA

RNA demethylases demethylate N6-methyladenosine RNA

Stable Identifier

R-HSA-8857692

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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RNA demethylases demethylate N6-methyladenosine RNA

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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 Feng, C, Liu, Y, Wang, G, Deng, Z, Zhang, Q, Wu, W, Tong, Y, Cheng, C, Chen, Z	J. Biol. Chem.	2014
24627050	FTO and obesity: mechanisms of association Zhao, X, Yang, Y, Sun, BF, Zhao, YL, Yang, YG	Curr. Diab. Rep.	2014
24778178	Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation Xu, C, Liu, K, Tempel, W, Demetriades, M, Aik, W, Schofield, CJ, Min, J	J. Biol. Chem.	2014
26788058	Role of FTO in Adipocyte Development and Function: Recent Insights Merkestein, M, Sellayah, D	Int J Endocrinol	2015
20376003	Crystal structure of the FTO protein reveals basis for its substrate specificity Han, Z, Niu, T, Chang, J, Lei, X, Zhao, M, Wang, Q, Cheng, W, Wang, J, Feng, Y, Chai, J	Nature	2010
22002720	N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO Jia, G, Fu, Y, Zhao, X, Dai, Q, Zheng, G, Yang, Y, Yi, C, Lindahl, T, Pan, T, Yang, YG, He, C	Nat. Chem. Biol.	2011
23177736	ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility Zheng, G, Dahl, JA, Niu, Y, Fedorcsak, P, Huang, CM, Li, CJ, Vågbø, CB, Shi, Y, Wang, WL, Song, SH, Lu, Z, Bosmans, RP, Dai, Q, Hao, YJ, Yang, X, Zhao, WM, Tong, WM, Wang, XJ, Bogdan, F, Furu, K, Fu, Y, Jia, G, Zhao, X, Liu, J, Krokan, HE, Klungland, A, Yang, YG, He, C	Mol. Cell	2013
17434869	A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity Frayling, TM, Timpson, NJ, Weedon, MN, Zeggini, E, Freathy, RM, Lindgren, CM, Perry, JR, Elliott, KS, Lango, H, Rayner, NW, Shields, B, Harries, LW, Barrett, JC, Ellard, S, Groves, CJ, Knight, B, Patch, AM, Ness, AR, Ebrahim, S, Lawlor, DA, Ring, SM, Ben-Shlomo, Y, Jarvelin, MR, Sovio, U, Bennett, AJ, Melzer, D, Ferrucci, L, Loos, RJ, Barroso, I, Wareham, NJ, Karpe, F, Owen, KR, Cardon, LR, Walker, M, Hitman, GA, Palmer, CN, Doney, AS, Morris, AD, Smith, GD, Hattersley, AT, McCarthy, MI	Science	2007
17496892	Variation in FTO contributes to childhood obesity and severe adult obesity Dina, C, Meyre, D, Gallina, S, Durand, E, Körner, A, Jacobson, P, Carlsson, LM, Kiess, W, Vatin, V, Lecoeur, C, Delplanque, J, Vaillant, E, Pattou, F, Ruiz, J, Weill, J, Levy-Marchal, C, Horber, F, Potoczna, N, Hercberg, S, Le Stunff, C, Bougnères, P, Kovacs, P, Marre, M, Balkau, B, Cauchi, S, Chèvre, JC, Froguel, P	Nat. Genet.	2007