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Biochemistry (Moscow)

, Volume 78, Issue 13, pp 1392–1404 | Cite as

Chemistry enters nucleic acids biology: Enzymatic mechanisms of RNA modification

  • S. Boschi-Muller
  • Y. MotorinEmail author
Review

Abstract

Modified nucleotides are universally conserved in all living kingdoms and are present in almost all types of cellular RNAs, including tRNA, rRNA, sn(sno)RNA, and mRNA and in recently discovered regulatory RNAs. Altogether, over 110 chemically distinct RNA modifications have been characterized and localized in RNA by various analytical methods. However, this impressive list of known modified nucleotides is certainly incomplete, mainly due to difficulties in identification and characterization of these particular residues in low abundance cellular RNAs. In DNA, modified residues are formed by both enzymatic reactions (like DNA methylations, for example) and by spontaneous chemical reactions resulting from oxidative damage. In contrast, all modified residues characterized in cellular RNA molecules are formed by specific action of dedicated RNA-modification enzymes, which recognize their RNA substrate with high specificity. These RNA-modification enzymes display a great diversity in terms of the chemical reaction and use various low molecular weight cofactors (or co-substrates) in enzymatic catalysis. Depending on the nature of the target base and of the co-substrate, precise chemical mechanisms are used for appropriate activation of the base and the co-substrate in the enzyme active site. In this review, we give an extended summary of the enzymatic mechanisms involved in formation of different methylated nucleotides in RNA, as well as pseudouridine residues, which are almost universally conserved in all living organisms. Other interesting mechanisms include thiolation of uridine residues by ThiI and the reaction of guanine exchange catalyzed by TGT. The latter implies the reversible cleavage of the N-glycosidic bond in order to replace the initially encoded guanine by an aza-guanosine base. Despite the extensive studies of RNA modification and RNA-modification machinery during the last 20 years, our knowledge on the exact chemical steps involved in catalysis of RNA modification remains very limited. Recent discoveries of radical mechanisms involved in base methylation clearly demonstrate that numerous possibilities are used in Nature for these difficult reactions. Future studies are certainly required for better understanding of the enzymatic mechanisms of RNA modification, and this knowledge is crucial not only for basic research, but also for development of new therapeutic molecules.

Key words

RNA-modification methylation pseudouridine catalytic mechanisms 

Abbreviations

MTase

methyltransferase

SAM/AdoMet

S-adenosyl-L-methionine

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References

  1. 1.
    Hocine, S., Singer, R. H., and Grunwald, D. (2010) Cold Spring Harbor Perspect. Biol., 2, a000752.CrossRefGoogle Scholar
  2. 2.
    Lamond, A. I. (1991) Curr. Opin. Cell Biol., 3, 493–501.PubMedCrossRefGoogle Scholar
  3. 3.
    Machnicka, M. A., Milanowska, K., Osman Oglou, O., Purta, E., Kurkowska, M., Olchowik, A., Januszewski, W., Kalinowski, S., Dunin-Horkawicz, S., Rother, K. M., et al. (2013) Nucleic Acids Res., 41, D262–267.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Helm, M. (2006) Nucleic Acids Res., 34, 721–733.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Motorin, Y., and Helm, M. (2011) Wiley Interdiscip. Rev. RNA, 2, 611–631.PubMedCrossRefGoogle Scholar
  6. 6.
    Motorin, Y., and Helm, M. (2010) Biochemistry, 49, 4934–4944.PubMedCrossRefGoogle Scholar
  7. 7.
    Ansmant, I., and Motorin, I. (2001) Mol. Biol., 35, 248–267.CrossRefGoogle Scholar
  8. 8.
    Schubert, H. L., Blumenthal, R. M., and Cheng, X. (2003) Trends Biochem. Sci., 28, 329–335.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Kozbial, P. Z., and Mushegian, A. R. (2005) BMC Struct. Biol., 5, 19.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Watanabe, K. (2005) J. Biol. Chem., 280, 10368–10377.PubMedCrossRefGoogle Scholar
  11. 11.
    Watanabe, K., Nureki, O., Fukai, S., Endo, Y., and Hori, H. (2006) J. Biol. Chem., 281, 34630–34639.PubMedCrossRefGoogle Scholar
  12. 12.
    Cheng, X., and Roberts, R. J. (2001) Nucleic Acids Res., 29, 3784–3795.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Hamdane, D., Argentini, M., Cornu, D., Myllykallio, H., Skouloubris, S., Hui-Bon-Hoa, G., and Golinelli-Pimpaneau, B. (2011) J. Biol. Chem., 286, 36268–36280.PubMedCrossRefGoogle Scholar
  14. 14.
    Hutcheson, R. U., and Broderick, J. B. (2012) Metallomics, 4, 1149–1154.PubMedCrossRefGoogle Scholar
  15. 15.
    Vey, J. L., and Drennan, C. L. (2011) Chem. Rev., 111, 2487–2506.PubMedCrossRefGoogle Scholar
  16. 16.
    Grove, T. L., Benner, J. S., Radle, M. I., Ahlum, J. H., Landgraf, B. J., Krebs, C., and Booker, S. J. (2011) Science, 332, 604–607.PubMedCrossRefGoogle Scholar
  17. 17.
    Noma, A., Kirino, Y., Ikeuchi, Y., and Suzuki, T. (2006) EMBO J., 25, 2142–2154.PubMedCrossRefGoogle Scholar
  18. 18.
    Hamma, T., and Ferre-D’Amare, A. R. (2006) Chem. Biol., 13, 1125–1135.PubMedCrossRefGoogle Scholar
  19. 19.
    Charette, M., and Gray, M. W. (2000) IUBMB Life, 49, 341–351.PubMedCrossRefGoogle Scholar
  20. 20.
    Mueller, E. G., and Ferre-D’Amare, A. R. (2009) in DNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution, Landes Biosciences, Austin, USA, pp. 363–376.Google Scholar
  21. 21.
    Ramamurthy, V., Swann, S. L., Paulson, J. L., Spedaliere, C. J., and Mueller, E. G. (1999) J. Biol. Chem., 274, 22225–22230.PubMedCrossRefGoogle Scholar
  22. 22.
    Motorin, Y., Keith, G., Simon, C., Foiret, D., Simos, G., Hurt, E., and Grosjean, H. (1998) RNA, 4, 856–869.PubMedCrossRefGoogle Scholar
  23. 23.
    Behm-Ansmant, I., Urban, A., Ma, X., Yu, Y.-T., Motorin, Y., and Branlant, C. (2003) RNA, 9, 1371–1382.PubMedCrossRefGoogle Scholar
  24. 24.
    Kittendorf, J. D. (2003) J. Biol. Chem., 278, 42369–42376.PubMedCrossRefGoogle Scholar
  25. 25.
    Kittendorf, J. D., Barcomb, L. M., Nonekowski, S. T., and Garcia, G. A. (2001) Biochemistry, 40, 14123–14133.PubMedCrossRefGoogle Scholar
  26. 26.
    Chervin, S. M., Kittendorf, J. D., and Garcia, G. A. (2007) Methods Enzymol., 425, 121–137.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Stengl, B., Reuter, K., and Klebe, G. (2005) Chembiochem, 6, 1926–1939.PubMedCrossRefGoogle Scholar
  28. 28.
    Rajakovich, L. J., Tomlinson, J., and Dos Santos, P. C. (2012) J. Bacteriol., 194, 4933–4940.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Palenchar, P. M., Buck, C. J., Cheng, H., Larson, T. J., and Mueller, E. G. (2000) J. Biol. Chem., 275, 8283–8286.PubMedCrossRefGoogle Scholar
  30. 30.
    Mueller, E. G., Palenchar, P. M., and Buck, C. J. (2001) J. Biol. Chem., 276, 33588–33595.PubMedCrossRefGoogle Scholar
  31. 31.
    Arragain, S., Handelman, S. K., Forouhar, F., Wei, F.-Y., Tomizawa, K., Hunt, J. F., Douki, T., Fontecave, M., Mulliez, E., and Atta, M. (2010) J. Biol. Chem., 285, 28425–28433.PubMedCrossRefGoogle Scholar
  32. 32.
    Meyer, S., Scrima, A., Versees, W., and Wittinghofer, A. (2008) J. Mol. Biol., 380, 532–547.PubMedCrossRefGoogle Scholar
  33. 33.
    Armengod, M.-E., Moukadiri, I., Prado, S., Ruiz-Partida, R., Benitez-Paez, A., Villarroya, M., Lomas, R., Garzon, M. J., Martinez-Zamora, A., Meseguer, S., et al. (2012) Biochimie, 94, 1510–1520.PubMedCrossRefGoogle Scholar
  34. 34.
    Osawa, T., Ito, K., Inanaga, H., Nureki, O., Tomita, K., and Numata, T. (2009) Structure, 17, 713–724.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhou, C., and Huang, R. H. (2008) Proc. Natl. Acad. Sci. USA, 105, 16142–16147.PubMedCrossRefGoogle Scholar
  36. 36.
    Hou, Y.-M., and Perona, J. J. (2010) FEBS Lett., 584, 278–286.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Guelorget, A., and Golinelli-Pimpaneau, B. (2011) Structure, 19, 282–291.PubMedCrossRefGoogle Scholar
  38. 38.
    Iwata-Reuyl, D. (2003) Bioorg. Chem., 31, 24–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Spedaliere, C. J., Ginter, J. M., Johnston, M. V., and Mueller, E. G. (2004) J. Am. Chem. Soc., 126, 12758–12759.PubMedCrossRefGoogle Scholar
  40. 40.
    Mueller, E. G. (2006) Nat. Chem. Biol., 2, 185–194.PubMedCrossRefGoogle Scholar
  41. 41.
    Motorin, Y., Lyko, F., and Helm, M. (2010) Nucleic Acids Res., 38, 1415–1430.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Behm-Ansmant, I., Helm, M., and Motorin, Y. (2011) J. Nucleic Acids, 2011, 408053.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Christian, T., Lahoud, G., Liu, C., Hoffmann, K., Perona, J. J., and Hou, Y.-M. (2010) RNA, 16, 2484–2492.PubMedCrossRefGoogle Scholar
  44. 44.
    Zheng, S., and Shuman, S. (2008) RNA, 14, 2297–2304.PubMedCrossRefGoogle Scholar
  45. 45.
    De la Pena, M., Kyrieleis, O. J. P., and Cusack, S. (2007) EMBO J., 26, 4913–4925.PubMedCrossRefGoogle Scholar
  46. 46.
    Maravic, G., Feder, M., Pongor, S., Flogel, M., and Bujnicki, J. M. (2003) J. Mol. Biol., 332, 99–109.PubMedCrossRefGoogle Scholar
  47. 47.
    Decroly, E., Debarnot, C., Ferron, F., Bouvet, M., Coutard, B., Imbert, I., Gluais, L., Papageorgiou, N., Sharff, A., Bricogne, G., et al. (2011) PLoS Pathog., 7, e1002059.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Hodel, A. E., Gershon, P. D., and Quiocho, F. A. (1998) Mol. Cell, 1, 443–447.PubMedCrossRefGoogle Scholar
  49. 49.
    Chan, C. M., Zhou, C., Brunzelle, J. S., and Huang, R. H. (2009) Proc. Natl. Acad. Sci. USA, 106, 17699–17704.CrossRefGoogle Scholar
  50. 50.
    Tkaczuk, K. L., Obarska, A., and Bujnicki, J. M. (2006) BMC Evol. Biol., 6, 6.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Huang, R. H. (2012) Biochemistry, 51, 4087–4095.PubMedCrossRefGoogle Scholar
  52. 52.
    Foster, P. G., Nunes, C. R., Greene, P., Moustakas, D., and Stroud, R. M. (2003) Structure, 11, 1609–1620.PubMedCrossRefGoogle Scholar
  53. 53.
    Lee, T. T., Agarwalla, S., and Stroud, R. M. (2005) Cell, 120, 599–611.PubMedCrossRefGoogle Scholar
  54. 54.
    Lee, T. T., Agarwalla, S., and Stroud, R. M. (2004) Structure, 12, 397–407.PubMedCrossRefGoogle Scholar
  55. 55.
    Nishimasu, H., Ishitani, R., Yamashita, K., Iwashita, C., Hirata, A., Hori, H., and Nureki, O. (2009) Proc. Natl. Acad. Sci. USA, 106, 8180–8185.PubMedCrossRefGoogle Scholar
  56. 56.
    Challand, M. R., Salvadori, E., Driesener, R. C., Kay, C. W. M., Roach, P. L., and Spencer, J. (2013) PloS One, 8, e67979.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Huang, L., Pookanjanatavip, M., Gu, X., and Santi, D. V. (1998) Biochemistry, 37, 344–351.PubMedCrossRefGoogle Scholar
  58. 58.
    Gu, X., Liu, Y., and Santi, D. V. (1999) Proc. Natl. Acad. Sci. USA, 96, 14270–14275.PubMedCrossRefGoogle Scholar
  59. 59.
    Miracco, E. J., and Mueller, E. G. (2011) J. Am. Chem. Soc., 133, 11826–11829.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Hamilton, C. S., Spedaliere, C. J., Ginter, J. M., Johnston, M. V., and Mueller, E. G. (2005) Arch. Biochem. Biophys., 433, 322–334.PubMedCrossRefGoogle Scholar
  61. 61.
    Phannachet, K., Elias, Y., and Huang, R. H. (2005) Biochemistry, 44, 15488–15494.PubMedCrossRefGoogle Scholar
  62. 62.
    Romier, C., Reuter, K., Suck, D., and Ficner, R. (1996) Biochemistry, 35, 15734–15739.PubMedCrossRefGoogle Scholar
  63. 63.
    Garcia, G. A., Chervin, S. M., and Kittendorf, J. D. (2009) Biochemistry, 48, 11243–11251.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Liu, Y., Zhu, X., Nakamura, A., Orlando, R., Soll, D., and Whitman, W. B. (2012) J. Biol. Chem., 287, 36683–36692.PubMedCrossRefGoogle Scholar
  65. 65.
    You, D., Xu, T., Yao, F., Zhou, X., and Deng, Z. (2008) Chembiochem, 9, 1879–1882.PubMedCrossRefGoogle Scholar
  66. 66.
    Zhou, J., Lv, C., Liang, B., Chen, M., Yang, W., and Li, H. (2010) J. Mol. Biol., 401, 690–695.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Wright, J. R., Keffer-Wilkes, L. C., Dobing, S. R., and Kothe, U. (2011) RNA, 17, 2074–2084.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Laboratoire IMoPA, UMR 7365 CNRS-UL, Faculté de Médecine de NancyUniversité de LorraineVandoeuvre les NancyFrance

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