Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases

Molecular Cell

Volumn 63, Issue 2, 2016, Pages 306-317

  Wang, Ping ^a,b   Doxtader, Katelyn A ^a,b   Nam, Yunsun ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HETERODIMER; METHYLTRANSFERASE; METTL14 PROTEIN; METTL3 PROTEIN; S ADENOSYLHOMOCYSTEINE; S ADENOSYLMETHIONINE; UNCLASSIFIED DRUG; ADENOSINE; METTL3 PROTEIN, HUMAN; METTL4 PROTEIN, HUMAN; N(6)-METHYLADENOSINE; PROTEIN BINDING; RNA;

ARTICLE; CATALYSIS; CONSENSUS SEQUENCE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME STABILITY; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; HUMAN; HUMAN CELL; IN VITRO STUDY; INTERACTIONS WITH RNA; MOLECULAR MODEL; MOLECULAR RECOGNITION; NONHUMAN; POINT MUTATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN MOTIF; STOICHIOMETRY; ALLOSTERISM; ANALOGS AND DERIVATIVES; BINDING SITE; CHEMISTRY; GENETICS; HEK293 CELL LINE; METABOLISM; METHYLATION; MUTATION; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION;

ADENOSINE; ALLOSTERIC REGULATION; BINDING SITES; CATALYTIC DOMAIN; HEK293 CELLS; HUMANS; METHYLATION; METHYLTRANSFERASES; MODELS, MOLECULAR; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; RNA; S-ADENOSYLHOMOCYSTEINE; S-ADENOSYLMETHIONINE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84978477054     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2016.05.041     Document Type: Article

References (47)

1. Adams, P.D., Afonine, P.V., Bunkóczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.-W., Kapral, G.J., Grosse-Kunstleve, R.W., et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 213–221.
2. Alarcón, C.R., Lee, H., Goodarzi, H., Halberg, N., Tavazoie, S.F., N6-methyladenosine marks primary microRNAs for processing. Nature 519 (2015), 482–485.
3. Bell, D.W., Novel genetic targets in endometrial cancer. Expert Opin. Ther. Targets 18 (2014), 725–730.
4. Ben-Haim, M.S., Moshitch-Moshkovitz, S., Rechavi, G., FTO: linking m6A demethylation to adipogenesis. Cell Res. 25 (2015), 3–4.
5. Bokar, J.A., Shambaugh, M.E., Polayes, D., Matera, A.G., Rottman, F.M., Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3 (1997), 1233–1247.
6. Brown, R.S., Zinc finger proteins: getting a grip on RNA. Curr. Opin. Struct. Biol. 15 (2005), 94–98.
7. Bujnicki, J.M., Feder, M., Radlinska, M., Blumenthal, R.M., Structure prediction and phylogenetic analysis of a functionally diverse family of proteins homologous to the MT-A70 subunit of the human mRNA:m(6)A methyltransferase. J. Mol. Evol. 55 (2002), 431–444.
8. Chen, T., Hao, Y.-J., Zhang, Y., Li, M.-M., Wang, M., Han, W., Wu, Y., Lv, Y., Hao, J., Wang, L., et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 16 (2015), 289–301.
9. Csepany, T., Lin, A., Baldick, C.J. Jr., Beemon, K., Sequence specificity of mRNA N6-adenosine methyltransferase. J. Biol. Chem. 265 (1990), 20117–20122.
10. 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. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485 (2012), 201–206.
11. Emsley, P., Cowtan, K., Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60 (2004), 2126–2132.
12. Forbes, S.A., Beare, D., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C., Ward, S., et al. COSMIC: exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res. 43 (2015), D805–D811.
13. 6A RNA methylation. Nat. Rev. Genet. 15 (2014), 293–306.
14. Fustin, J.M., Doi, M., Yamaguchi, Y., Hida, H., Nishimura, S., Yoshida, M., Isagawa, T., Morioka, M.S., Kakeya, H., Manabe, I., Okamura, H., RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155 (2013), 793–806.
15. Geula, S., Moshitch-Moshkovitz, S., Dominissini, D., Mansour, A.A., Kol, N., Salmon-Divon, M., Hershkovitz, V., Peer, E., Mor, N., Manor, Y.S., et al. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347 (2015), 1002–1006.
16. Guja, K.E., Venkataraman, K., Yakubovskaya, E., Shi, H., Mejia, E., Hambardjieva, E., Karzai, A.W., Garcia-Diaz, M., Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1. Nucleic Acids Res. 41 (2013), 7947–7959.
17. Hall, T.M., Multiple modes of RNA recognition by zinc finger proteins. Curr. Opin. Struct. Biol. 15 (2005), 367–373.
18. Harper, J.E., Miceli, S.M., Roberts, R.J., Manley, J.L., Sequence specificity of the human mRNA N6-adenosine methylase in vitro. Nucleic Acids Res. 18 (1990), 5735–5741.
19. Iyer, L.M., Zhang, D., Aravind, L., Adenine methylation in eukaryotes: apprehending the complex evolutionary history and functional potential of an epigenetic modification. BioEssays 38 (2016), 27–40.
20. Jia, D., Jurkowska, R.Z., Zhang, X., Jeltsch, A., Cheng, X., Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449 (2007), 248–251.
21. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.-G.G., He, C., N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7 (2011), 885–887.
22. Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26 (1993), 283–291.
23. Li, F., Kennedy, S., Hajian, T., Gibson, E., Seitova, A., Xu, C., Arrowsmith, C.H., Vedadi, M., A Radioactivity-based assay for screening human m6A-RNA methyltransferase, METTL3-METTL14 complex, and demethylase ALKBH5. J. Biomol. Screen. 21 (2016), 290–297.
24. Liu, N., Pan, T., N6-methyladenosine-encoded epitranscriptomics. Nat. Struct. Mol. Biol. 23 (2016), 98–102.
25. Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X., et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10 (2014), 93–95.
26. 6A methyltransferases and demethylases and biochemical characterization of their catalytic activity. Methods Enzymol. 560 (2015), 117–130.
27. Liu, N., Dai, Q., Zheng, G., He, C., Parisien, M., Pan, T., N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518 (2015), 560–564.
28. Lunde, B.M., Moore, C., Varani, G., RNA-binding proteins: modular design for efficient function. Nat. Rev. Mol. Cell Biol. 8 (2007), 479–490.
29. Meyer, K.D., Jaffrey, S.R., The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat. Rev. Mol. Cell Biol. 15 (2014), 313–326.
30. Meyer, K.D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C.E., Jaffrey, S.R., Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149 (2012), 1635–1646.
31. Minor, W., Cymborowski, M., Otwinowski, Z., Chruszcz, M., HKL-3000: the integration of data reduction and structure solution—from diffraction images to an initial model in minutes. Acta Crystallogr. D Biol. Crystallogr. 62 (2006), 859–866.
32. Morin, A., Eisenbraun, B., Key, J., Sanschagrin, P.C., Timony, M.A., Ottaviano, M., Sliz, P., Collaboration gets the most out of software. eLife, 2, 2013, e01456.
33. Peng, L., Yuan, X., Jiang, B., Tang, Z., Li, G.C., LncRNAs: key players and novel insights into cervical cancer. Tumour Biol. 37 (2016), 2779–2788.
34. 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. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24 (2014), 177–189.
35. Rottman, F.M., Bokar, J.A., Narayan, P., Shambaugh, M.E., Ludwiczak, R., N6-adenosine methylation in mRNA: substrate specificity and enzyme complexity. Biochimie 76 (1994), 1109–1114.
36. Schibler, U., Kelley, D.E., Perry, R.P., Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J. Mol. Biol. 115 (1977), 695–714.
37. Schwartz, S., Mumbach, M.R., Jovanovic, M., Wang, T., Maciag, K., Bushkin, G.G., Mertins, P., Ter-Ovanesyan, D., Habib, N., Cacchiarelli, D., et al. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Rep. 8 (2014), 284–296.
38. Song, J., Teplova, M., Ishibe-Murakami, S., Patel, D.J., Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335 (2012), 709–712.
39. Studier, F.W., Protein production by auto-induction in high density shaking cultures. Protein Expr. Purif. 41 (2005), 207–234.
40. Thomas, C.B., Scavetta, R.D., Gumport, R.I., Churchill, M.E.A., Structures of liganded and unliganded RsrI N6-adenine DNA methyltransferase: a distinct orientation for active cofactor binding. J. Biol. Chem. 278 (2003), 26094–26101.
41. Wallace, A.C., Laskowski, R.A., Thornton, J.M., LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 8 (1995), 127–134.
42. Wang, X., Lu, Z., Gomez, A., Hon, G.C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G., et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505 (2014), 117–120.
43. Wang, Y., Li, Y., Toth, J.I., Petroski, M.D., Zhang, Z., Zhao, J.C., N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16 (2014), 191–198.
44. Wang, X., Zhao, B.S., Roundtree, I.A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., He, C., N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 161 (2015), 1388–1399.
45. Yang, H., Wang, Z., Shen, Y., Wang, P., Jia, X., Zhao, L., Zhou, P., Gong, R., Li, Z., Yang, Y., et al. Crystal structure of the nosiheptide-resistance methyltransferase of Streptomyces actuosus. Biochemistry 49 (2010), 6440–6450.
46. Zheng, G., Dahl, J.A., Niu, Y., Fedorcsak, P., Huang, C.-M., Li, C.J., Vågbø, C.B., Shi, Y., Wang, W.-L., Song, S.-H., et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49 (2013), 18–29.
47. Zhou, K.I., Parisien, M., Dai, Q., Liu, N., Diatchenko, L., Sachleben, J.R., Pan, T., N(6)-methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding. J. Mol. Biol. 428:5 Pt A (2016), 822–833.