Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5

Nucleic Acids Research

Volumn 43, Issue 1, 2015, Pages 373-384

  Huang, Yue ^a   Yan, Jingli ^b   Li, Qi ^a   Li, Jiafei ^a   Gong, Shouzhe ^a   Zhou, Hu ^a   Gan, Jianhua ^c   Jiang, Hualiang ^a   Jia, Gui Fang ^b   Luo, Cheng ^a   Yang, Cai Guang ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b PEKING UNIVERSITY   (China)

^c FUDAN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ALKBH5 PROTEIN, HUMAN; DIOXYGENASE; ENZYME INHIBITOR; FTO PROTEIN, HUMAN; MECLOFENAMIC ACID; MEMBRANE PROTEIN; MESSENGER RNA; N(6)-METHYLADENOSINE; NONSTEROID ANTIINFLAMMATORY AGENT; PROTEIN; SINGLE STRANDED DNA;

ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BINDING COMPETITION; CHEMISTRY; HELA CELL LINE; HUMAN; METABOLISM; STRUCTURE ACTIVITY RELATION;

ADENOSINE; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BINDING, COMPETITIVE; DIOXYGENASES; DNA, SINGLE-STRANDED; ENZYME INHIBITORS; HELA CELLS; HUMANS; MECLOFENAMIC ACID; MEMBRANE PROTEINS; PROTEINS; RNA, MESSENGER; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84942253294     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gku1276     Document Type: Article

References (67)

1. Desrosiers, R., Friderici, K., Rottman, F. (1974) Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl Acad. Sci. U.S.A., 71, 3971-3975.
2. Wei, C.M., Gershowitz, A., Moss, B. (1975) Methylated nucleotides block 5-terminus of HeLa cell messenger RNA. Cell, 4, 379-386.
3. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.G. et al. (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol., 7, 885-887.
4. Ping, X.L., Sun, B.F., Wang, L., Xiao, W., Yang, X., Wang, W.J., Adhikari, S., Shi, Y., Lv, Y., Chen, Y.S. et al. (2014) Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res., 24, 177-189.
5. Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X. et al. (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol., 10, 93-95.
6. Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M. et al. (2012) Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485, 201-206.
7. Meyer, K.D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C.E., Jaffrey, S.R. (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3-UTRs and near stop codons. Cell, 149, 1635-1646.
8. Wang, X., Lu, Z., Gomez, A., Hon, G.C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G. et al. (2014) N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 505, 117-120.
9. Schwartz, S., Agarwala, S.D., Mumbach, M.R., Jovanovic, M., Mertins, P., Shishkin, A., Tabach, Y., Mikkelsen, T.S., Satija, R., Ruvkun, G. et al. (2013) High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell, 155, 1409-1421.
10. Jia, G., Fu, Y., He, C. (2013) Reversible RNA adenosine methylation in biological regulation. Trends Genet., 29, 108-115.
11. Niu, Y., Zhao, X., Wu, Y.S., Li, M.M., Wang, X.J., Yang, Y.G. (2013) N6-methyl-adenosine (m6A) in RNA: an old modification with a novel epigenetic function. Genomics Proteomics Bioinformatics, 11, 8-17.
12. 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.
13. Zhao, X., Yang, Y., Sun, B.F., Zhao, Y.L., Yang, Y.G. (2014) FTO and obesity: mechanisms of association. Curr. Diab. Rep., 14, 486.
14. Jia, G., Yang, C.G., Yang, S., Jian, X., Yi, C., Zhou, Z., 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.
15. Sedgwick, B. (2004) Repairing DNA-methylation damage. Nat. Rev. Mol. Cell Biol., 5, 148-157.
16. Drablos, F., Feyzi, E., Aas, P.A., Vaagbo, C.B., Kavli, B., Bratlie, M.S., Pena-Diaz, J., Otterlei, M., Slupphaug, G., Krokan, H.E. (2004) Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair, 3, 1389-1407.
17. Mishina, Y., Duguid, E.M., He, C. (2006) Direct reversal of DNA alkylation damage. Chem. Rev., 106, 215-232.
18. Falnes, P.O., Klungland, A., Alseth, I. (2007) Repair of methyl lesions in DNA and RNA by oxidative demethylation. Neuroscience, 145, 1222-1232.
19. Li, D., Delaney, J.C., Page, C.M., Yang, X., Chen, A.S., Wong, C., Drennan, C.L., Essigmann, J.M. (2012) Exocyclic carbons adjacent to the N6 of adenine are targets for oxidation by the Escherichia coli adaptive response protein AlkB. J. Am. Chem. Soc., 134, 8896-8901.
20. 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.
21. Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Bruning, J.C., Ruther, U. (2009) Inactivation of the Fto gene protects from obesity. Nature, 458, 894-898.
22. Pausova, Z., Syme, C., Abrahamowicz, M., Xiao, Y., Leonard, G.T., Perron, M., Richer, L., Veillette, S., Smith, G.D., Seda, O. et al. (2009) A common variant of the FTO gene is associated with not only increased adiposity but also elevated blood pressure in French Canadians. Circ. Cardiovasc. Genet., 2, 260-269.
23. Wehr, E., Schweighofer, N., Moller, R., Giuliani, A., Pieber, T.R., Obermayer-Pietsch, B. (2010) Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome. Metabolism, 59, 575-580.
24. Keller, L., Xu, W., Wang, H.X., Winblad, B., Fratiglioni, L., Graff, C. (2011) The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer's disease risk: a prospective cohort study. J. Alzheimers Dis., 23, 461-469.
25. Kaklamani, V., Yi, N., Sadim, M., Siziopikou, K., Zhang, K., Xu, Y., Tofilon, S., Agarwal, S., Pasche, B., Mantzoros, C. (2011) The role of the fat mass and obesity associated gene (FTO) in breast cancer risk. BMC Med. Genet., 12, 52.
26. Shen, F., Huang, W., Huang, J.T., Xiong, J., Yang, Y., Wu, K., Jia, G.F., Chen, J., Feng, Y.Q., Yuan, B.F. et al. (2014) Decreased N(6)-methyladenosine in peripheral blood RNA from Diabetic Patients Is Associated with FTO Expression Rather than ALKBH5. J. Clin. Endocrinol. Metab., doi:jc20141893.
27. Zheng, G., Dahl, J.A., Niu, Y., Fedorcsak, P., Huang, C.M., Li, C.J., Vagbo, C.B., Shi, Y., Wang, W.L., Song, S.H. et al. (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell, 49, 18-29.
28. He, C. (2010) Grand challenge commentary: RNA epigenetics? Nat. Chem. Biol., 6, 863-865.
29. Liu, N., Pan, T. (2014) RNA epigenetics. Transl. Res., doi:10.1016/j.trsl.2014.04.003.
30. Falnes, P.O., Johansen, R.F., Seeberg, E. (2002) AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature, 419, 178-182.
31. Trewick, S.C., Henshaw, T.F., Hausinger, R.P., Lindahl, T., Sedgwick, B. (2002) Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature, 419, 174-178.
32. Zhu, C., Yi, C. (2014) Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues. Angew. Chem. Int. Ed. Engl., 53, 3659-3662.
33. Ougland, R., Zhang, C.M., Liiv, A., Johansen, R.F., Seeberg, E., Hou, Y.M., Remme, J., Falnes, P.O. (2004) AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Mol. Cell, 16, 107-116.
34. Fu, Y., Dai, Q., Zhang, W., Ren, J., Pan, T., He, C. (2010) The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the wobble position of tRNA. Angew. Chem. Int. Ed. Engl., 49, 8885-8888.
35. Aas, P.A., Otterlei, M., Falnes, P.O., Vagbo, C.B., Skorpen, F., Akbari, M., Sundheim, O., Bjoras, M., Slupphaug, G., Seeberg, E. et al. (2003) Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature, 421, 859-863.
36. Ringvoll, J., Nordstrand, L.M., Vagbo, C.B., Talstad, V., Reite, K., Aas, P.A., Lauritzen, K.H., Liabakk, N.B., Bjork, A., Doughty, R.W. et al. (2006) Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO J., 25, 2189-2198.
37. Kruidenier, L., Chung, C.W., Cheng, Z., Liddle, J., Che, K., Joberty, G., Bantscheff, M., Bountra, C., Bridges, A., Diallo, H. et al. (2012) A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature, 488, 404-408.
38. Luo, X., Liu, Y., Kubicek, S., Myllyharju, J., Tumber, A., Ng, S., Che, K.H., Podoll, J., Heightman, T.D., Oppermann, U. et al. (2011) A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases. J. Am. Chem. Soc., 133, 9451-9456.
39. Woon, E.C., Tumber, A., Kawamura, A., Hillringhaus, L., Ge, W., Rose, N.R., Ma, J.H., Chan, M.C., Walport, L.J., Che, K.H. et al. (2012) Linking of 2-oxoglutarate and substrate binding sites enables potent and highly selective inhibition of JmjC histone demethylases. Angew. Chem. Int. Ed. Engl., 51, 1631-1634.
40. Woon, E.C., Demetriades, M., Bagg, E.A., Aik, W., Krylova, S.M., Ma, J.H., Chan, M., Walport, L.J., Wegman, D.W., Dack, K.N. et al. (2012) Dynamic combinatorial mass spectrometry leads to inhibitors of a 2-oxoglutarate-dependent nucleic acid demethylase. J. Med. Chem., 55, 2173-2184.
41. Zheng, G., Cox, T., Tribbey, L., Wang, G.Z., Iacoban, P., Booher, M.E., Gabriel, G.J., Zhou, L., Bae, N., Rowles, J. et al. (2014) Synthesis of a FTO inhibitor with anticonvulsant activity. ACS Chem. Neurosci., 5, 658-665.
42. Chen, B., Ye, F., Yu, L., Jia, G., Huang, X., Zhang, X., Peng, S., Chen, K., Wang, M., Gong, S. et al. (2012) Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor. J. Am. Chem. Soc., 134, 17963-17971.
43. Rose, N.R., McDonough, M.A., King, O.N., Kawamura, A., Schofield, C.J. (2011) Inhibition of 2-oxoglutarate dependent oxygenases. Chem. Soc. Rev., 40, 4364-4397.
44. Aik, W., Demetriades, M., Hamdan, M.K., Bagg, E.A., Yeoh, K.K., Lejeune, C., Zhang, Z., McDonough, M.A., Schofield, C.J. (2013) Structural basis for inhibition of the fat mass and obesity associated protein (FTO). J. Med. Chem., 56, 3680-3688.
45. Toh, Joel D.W., Sun, L., Lau, Lisa Z. M., Tan, Jackie, Low, Joanne J. A., Tang, Colin W. Q., Cheong, Eleanor J. Y., Tan, Melissa J. H., Chen, Yun, Hong, Wanjin et al. (2014) A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N6-methyladenosine demethylase FTO. Chem. Sci., doi:10.1039/C4SC02554G.
46. Aik, W., Scotti, J.S., Choi, H., Gong, L., Demetriades, M., Schofield, C.J., McDonough, M.A. (2014) Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Nucleic Acids Res., 42, 4741-4754.
47. Niesen, F.H., Berglund, H., Vedadi, M. (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc., 2, 2212-2221.
48. Otwinowski, Z., Minor, W. (1997) Methods in Enzymology. In: Macromolecular Crystallography, Patr A, Vol. 276, pp. 307-326.
49. Collaborative Computational Project, Number 4. (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr., 50, 760-763.
50. Read, R.J. (2001) Pushing the boundaries of molecular replacement with maximum likelihood. Acta Crystallogr. D Biol. Crystallogr., 57, 1373-1382.
51. Emsley, P., Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr., 60, 2126-2132.
52. Murshudov, G.N., Vagin, A.A., Dodson, E.J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr., 53, 240-255.
53. Chen, B., Liu, H., Sun, X., Yang, C.G. (2010) Mechanistic insight into the recognition of single-stranded and double-stranded DNA substrates by ABH2 and ABH3. Mol. Biosyst., 6, 2143-2149.
54. Vedadi, M., Niesen, F.H., Allali-Hassani, A., Fedorov, O.Y., Finerty, P.J. Jr, Wasney, G.A., Yeung, R., Arrowsmith, C., Ball, L.J., Berglund, H. et al. (2006) Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc. Natl Acad. Sci. U.S.A., 103, 15835-15840.
55. Niesen, F.H., Berglund, H., Vedadi, M. (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc., 2, 2212-2221.
56. Kovala-Demertzi, D., Staninska, M., Garcia-Santos, I., Castineiras, A., Demertzis, M.A. (2011) Synthesis, crystal structures and spectroscopy of meclofenamic acid and its metal complexes with manganese(II), copper(II), zinc(II) and cadmium(II). Antiproliferative and superoxide dismutase activity. J. Inorg. Biochem., 105, 1187-1195.
57. Yu, B., Edstrom, W.C., Benach, J., Hamuro, Y., Weber, P.C., Gibney, B.R., Hunt, J.F. (2006) Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB. Nature, 439, 879-884.
58. Sundheim, O., Vagbo, C.B., Bjoras, M., Sousa, M.M., Talstad, V., Aas, P.A., Drablos, F., Krokan, H.E., Tainer, J.A., Slupphaug, G. (2006) Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J., 25, 3389-3397.
59. Yang, C.G., Yi, C., Duguid, E.M., Sullivan, C.T., Jian, X., Rice, P.A., He, C. (2008) Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature, 452, 961-965.
60. Han, Z., Niu, T., Chang, J., Lei, X., Zhao, M., Wang, Q., Cheng, W., Wang, J., Feng, Y., Chai, J. (2010) Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature, 464, 1205-1209.
61. Yi, C., Chen, B., Qi, B., Zhang, W., Jia, G., Zhang, L., Li, C.J., Dinner, A.R., Yang, C.G., He, C. (2012) Duplex interrogation by a direct DNA repair protein in search of base damage. Nat. Struct. Mol. Biol., 19, 671-676.
62. Chen, B., Gan, J.H., Yang, C.G. (2014) The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of-hairpin. Sci. China Chem., 57, 307-313.
63. Xu, C., Liu, K., Tempel, W., Demetriades, M., Aik, W., Schofield, C.J., Min, J. (2014) Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation. J. Biol. Chem., 289, 17299-17311.
64. Feng, C., Liu, Y., Wang, G., Deng, Z., Zhang, Q., Wu, W., Tong, Y., Cheng, C., Chen, Z. (2014) Crystal structures of the human RNA demethylase alkbh5 reveal basis for substrate recognition. J. Biol. Chem., 289, 11571-11583.
65. Chen, W., Zhang, L., Zheng, G., Fu, Y., Ji, Q., Liu, F., Chen, H., He, C. (2014) Crystal structure of the RNA demethylase ALKBH5 from zebrafish. FEBS Lett., 588, 892-898.
66. Shen, L., Song, C.X., He, C., Zhang, Y. (2014) Mechanism and function of oxidative reversal of DNA and RNA methylation. Annu. Rev. Biochem., 83, 585-614.
67. Bartzatt, R. (2012) Anti-inflammatory drugs and prediction of new structures by comparative analysis. Antiinflamm Antiallergy Agents Med. Chem., 11, 151-160.