Kinetic analysis of FTO (fat mass and obesity-associated) reveals that it is unlikely to function as a sensor for 2-oxoglutarate

Biochemical Journal

Volumn 444, Issue 2, 2012, Pages 183-187

  Ma, Marcella ^a,b   Harding, Heather P ^a,b   O'Rahilly, Stephen ^a,b   Ron, David ^a,b   Yeo, Giles S H ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b ADDENBROOKE S HOSPITAL   (United Kingdom)

Author keywords

2 oxoglutarate; Demethylation; Fat mass and obesity associated (FTO); Obesity; RNase A; Single nucleotide polymorphism

Indexed keywords

2 OXOGLUTARIC ACID; CITRIC ACID; DIOXYGENASE; FAT MASS AND OBESITY ASSOCIATED PROTEIN; RIBONUCLEASE A; UNCLASSIFIED DRUG;

ARTICLE; BODY MASS; CATALYSIS; CONTROLLED STUDY; DEMETHYLATION; ENZYME ACTIVITY; ENZYME KINETICS; FLUORESCENCE; GENETIC ASSOCIATION; PRIORITY JOURNAL; RNA CLEAVAGE; SINGLE NUCLEOTIDE POLYMORPHISM;

BIOSENSING TECHNIQUES; BODY MASS INDEX; DNA METHYLATION; HUMANS; KETOGLUTARIC ACIDS; KINETICS; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; REPRODUCIBILITY OF RESULTS; SUBSTRATE SPECIFICITY;

EID: 84860871770     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20120065     Document Type: Article

References (23)

1. Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R., Elliott, K. S., Lango, H., Rayner, N. W. et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894 (Pubitemid 46764279)
2. Tung, Y. C. and Yeo, G. S. (2011) From GWAS to biology: lessons from FTO. Ann. N. Y. Acad. Sci. 1220, 162-171
3. Gerken, T., Girard, C. A., Tung, Y. C., Webby, C. J., Saudek, V., Hewitson, K. S., Yeo, G. S., McDonough, M. A., Cunliffe, S., McNeill, L. A. et al. (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318, 1469-1472 (Pubitemid 350208961)
4. Tung, Y. C., Ayuso, E., Shan, X., Bosch, F., O'Rahilly, S., Coll, A. P. and Yeo, G. S. (2010) Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS ONE 5, e8771
5. Jia, G., Yang, C. G., Yang, S., Jian, X., Yi, C., Zhou, Z. and He, C. (2008) Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582, 3313-3319
6. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y. G. and He, C. (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885-887
7. Han, Z., Niu, T., Chang, J., Lei, X., Zhao, M., Wang, Q., Cheng, W., Wang, J., Feng, Y. and Chai, J. (2010) Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464, 1205-1209
8. Boissel, S., Reish, O., Proulx, K., Kawagoe-Takaki, H., Sedgwick, B., Yeo, G. S., Meyre, D., Golzio, C., Molinari, F., Kadhom, N. et al. (2009) Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am. J. Hum. Genet. 85, 106-111
9. Meyre, D., Proulx, K., Kawagoe-Takaki, H., Vatin, V., Gutierrez-Aguilar, R., Lyon, D., Ma, M., Choquet, H., Horber, F., Van Hul, W. et al. (2010) Prevalence of loss-of-function FTO mutations in lean and obese individuals. Diabetes 59, 311-318
10. delCardayre, S. B. and Raines, R. T. (1995) A residue to residue hydrogen bond mediates the nucleotide specificity of ribonuclease A. J. Mol. Biol. 252, 328-336
11. Fisher, B. M., Schultz, L. W. and Raines, R. T. (1998) Coulombic effects of remote subsites on the active site of ribonuclease A. Biochemistry 37, 17386-17401 (Pubitemid 29013740)
12. Kim, S. E., Gorrell, A., Rader, S. D. and Lee, C. H. (2010) Endoribonuclease activity of human apurinic/apyrimidinic endonuclease 1 revealed by a real-time fluorometric assay. Anal. Biochem. 398, 69-75
13. Li, J. J., Geyer, R. and Tan, W. (2000) Using molecular beacons as a sensitive fluorescence assay for enzymatic cleavage of single-stranded DNA. Nucleic Acids Res. 28, E52
14. Rizzo, J., Gifford, L. K., Zhang, X., Gewirtz, A. M. and Lu, P. (2002) Chimeric RNA-DNA molecular beacon assay for ribonuclease H activity. Mol. Cell. Probes 16, 277-283
15. Church, C., Lee, S., Bagg, E. A., McTaggart, J. S., Deacon, R., Gerken, T., Lee, A., Moir, L., Mecinovic, J., Quwailid, M. M. et al. (2009) A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet. 5, e1000599
16. Church, C., Moir, L., McMurray, F., Girard, C., Banks, G. T., Teboul, L., Wells, S., Bruning, J. C., Nolan, P. M., Ashcroft, F. M. and Cox, R. D. (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat. Genet. 42, 1086-1092
17. Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Bruning, J. C. and Ruther, U. (2009) Inactivation of the Fto gene protects from obesity. Nature 458, 894-898
18. Gao, X., Shin, Y. H., Li, M., Wang, F., Tong, Q. and Zhang, P. (2010) The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice. PLoS ONE 5, e14005
19. Muhling, J., Tussing, F., Nickolaus, K. A., Matejec, R., Henrich, M., Harbach, H., Wolff, M., Weismuller, K., Engel, J., Welters, I. D. et al. (2010) Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production. Amino Acids 38, 167-177
20. Kanelakis, K. C., Palomino, H. L., Li, L., Wu, J., Yan, W., Rosen, M. D., Rizzolio, M. C., Trivedi, M., Morton, M. F., Yang, Y. et al. (2009) Characterization of a robust enzymatic assay for inhibitors of 2-oxoglutarate-dependent hydroxylases. J. Biomol. Screening 14, 627-635
21. Hewitson, K. S., McNeill, L. A., Riordan, M. V., Tian, Y. M., Bullock, A. N., Welford, R. W., Elkins, J. M., Oldham, N. J., Bhattacharya, S., Gleadle, J. M. et al. (2002) Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277, 26351-26355 (Pubitemid 34967127)
22. Kowalak, J. A., Pomerantz, S. C., Crain, P. F. and McCloskey, J. A. (1993) A novel method for the determination of post-transcriptional modification in RNA by mass spectrometry. Nucleic Acids Res. 21, 4577-4585 (Pubitemid 23292724)
23. Desrosiers, R., Friderici, K. and Rottman, F. (1974) Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl. Acad. Sci. U.S.A. 71, 3971-3975