The Interaction Between L7Ae Family of Proteins and RNA Kink Turns

  • Lin Huang
  • David M. J. LilleyEmail author
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


The L7Ae superfamily of proteins are widespread, with important roles in the ribosome, snoRNP structures, and spliceosome assembly. They bind extremely tightly and selectively to k-turn structures in RNA. An alpha helix is placed in the widened major groove on the outside of the RNA kink in order to make both sequence-specific and non-specific interactions. The interaction is disrupted by N6-methylation of adenine at a specific position, and this can modulate the assembly of human box C/D snoRNP. L7Ae-k-turn complexes can be used in nanoconstruction to generate a variety of molecular objects.


  1. 1.
    Ban, N., Nissen, P., Hansen, J., Moore, P. B., & Steitz, T. A. (2000). The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science, 289, 905–920.ADSCrossRefGoogle Scholar
  2. 2.
    Vidovic, I., Nottrott, S., Hartmuth, K., Luhrmann, R., & Ficner, R. (2000). Crystal structure of the spliceosomal 15.5 kD protein bound to a U4 snRNA fragment. Molecular Cell, 6, 1331–1342.CrossRefGoogle Scholar
  3. 3.
    Wozniak, A. K., Nottrott, S., Kuhn-Holsken, E., Schroder, G. F., Grubmuller, H., Luhrmann, R., et al. (2005). Detecting protein-induced folding of the U4 snRNA kink-turn by single-molecule multiparameter FRET measurements. RNA, 11, 1545–1554.CrossRefGoogle Scholar
  4. 4.
    Montange, R. K., & Batey, R. T. (2006). Structure of the S-adenosylmethionine riboswitch regulatory mRNA element. Nature, 441, 1172–1175.ADSCrossRefGoogle Scholar
  5. 5.
    Blouin, S., & Lafontaine, D. A. (2007). A loop loop interaction and a K-turn motif located in the lysine aptamer domain are important for the riboswitch gene regulation control. RNA, 13, 1256–12567.CrossRefGoogle Scholar
  6. 6.
    Smith, K. D., Lipchock, S. V., Ames, T. D., Wang, J., Breaker, R. R., & Strobel, S. A. (2009). Structural basis of ligand binding by a c-di-GMP riboswitch. Nature Structural and Molecular Biology, 16, 1218–1223.CrossRefGoogle Scholar
  7. 7.
    Peselis, A., & Serganov, A. (2012). Structural insights into ligand binding and gene expression control by an adenosylcobalamin riboswitch. Nature Structural and Molecular Biology, 19, 1182–1184.CrossRefGoogle Scholar
  8. 8.
    Baird, N. J., & Ferre-D’Amare, A. R. (2013). Modulation of quaternary structure and enhancement of ligand binding by the K-turn of tandem glycine riboswitches. RNA, 19, 167–176.CrossRefGoogle Scholar
  9. 9.
    Zhang, J., & Ferre-D’Amare, A. R. (2013). Co-crystal structure of a T-box riboswitch stem I domain in complex with its cognate tRNA. Nature, 500, 363–366.ADSCrossRefGoogle Scholar
  10. 10.
    Moore, T., Zhang, Y., Fenley, M. O., & Li, H. (2004). Molecular basis of box C/D RNA-protein interactions; Cocrystal structure of archaeal L7Ae and a box C/D RNA. Structure, 12, 807–818.CrossRefGoogle Scholar
  11. 11.
    Hamma, T., & Ferré-D’Amaré, A. R. (2004). Structure of protein L7Ae bound to a K-turn derived from an archaeal box H/ACA sRNA at 1.8 Å resolution. Structure, 12, 893–903.CrossRefGoogle Scholar
  12. 12.
    Szewczak, L. B., Gabrielsen, J. S., Degregorio, S. J., Strobel, S. A., & Steitz, J. A. (2005). Molecular basis for RNA kink-turn recognition by the h15.5 K small RNP protein. RNA, 11, 1407–1419.CrossRefGoogle Scholar
  13. 13.
    Youssef, O. A., Terns, R. M., & Terns, M. P. (2007). Dynamic interactions within sub-complexes of the H/ACA pseudouridylation guide RNP. Nucleic Acids Research, 35, 6196–6206.CrossRefGoogle Scholar
  14. 14.
    Schroeder, K. T., & Lilley, D. M. (2009). Ion-induced folding of a kink turn that departs from the conventional sequence. Nucleic Acids Research, 37, 7281–7289.CrossRefGoogle Scholar
  15. 15.
    Schroeder, K. T., Daldrop, P., McPhee, S. A., & Lilley, D. M. (2012). Structure and folding of a rare, natural kink turn in RNA with an A·A pair at the 2b·2n position. RNA, 18, 1257–1266.CrossRefGoogle Scholar
  16. 16.
    Wang, J., Daldrop, P., Huang, L., & Lilley, D. M. (2014). The k-junction motif in RNA structure. Nucleic Acids Research, 42, 5322–5331.CrossRefGoogle Scholar
  17. 17.
    McPhee, S. A., Huang, L., & Lilley, D. M. (2014). A critical base pair in k-turns that confers folding characteristics and correlates with biological function. Nature comm., 5, 5127.ADSCrossRefGoogle Scholar
  18. 18.
    Turner, B., Melcher, S. E., Wilson, T. J., Norman, D. G., & Lilley, D. M. J. (2005). Induced fit of RNA on binding the L7Ae protein to the kink-turn motif. RNA, 11, 1192–1200.CrossRefGoogle Scholar
  19. 19.
    Schroeder, K. T., Daldrop, P., & Lilley, D. M. J. (2011). RNA tertiary interactions in a riboswitch stabilize the structure of a kink turn. Structure, 19, 1233–1240.CrossRefGoogle Scholar
  20. 20.
    Nissen, P., Ippolito, J. A., Ban, N., Moore, P. B., & Steitz, T. A. (2001). RNA tertiary interactions in the large ribosomal subunit: The A-minor motif. Proceedings of the National Academy of Sciences of the United States of America, 98, 4899–4903.ADSCrossRefGoogle Scholar
  21. 21.
    Liu, J., & Lilley, D. M. J. (2007). The role of specific 2′-hydroxyl groups in the stabilization of the folded conformation of kink-turn RNA. RNA, 13, 200–210.CrossRefGoogle Scholar
  22. 22.
    Daldrop, P., & Lilley, D. M. J. (2013). The plasticity of a structural motif in RNA: Structural polymorphism of a kink turn as a function of its environment. RNA, 19, 357–364.CrossRefGoogle Scholar
  23. 23.
    Huang L, Wang J, Lilley DMJ (2016) A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function. Nucleic Acids Research.Google Scholar
  24. 24.
    Koonin, E. V., Bork, P., & Sander, C. (1994). A novel RNA-binding motif in omnipotent suppressors of translation termination, ribosomal proteins and a ribosome modification enzyme? Nucleic Acids Research, 22, 2166–2167.CrossRefGoogle Scholar
  25. 25.
    Watkins, N. J., Segault, V., Charpentier, B., Nottrott, S., Fabrizio, P., Bachi, A., et al. (2000). A common core RNP structure shared between the small nucleolar box C/D RNPs and the spliceosomal U4 snRNP. Cell, 103, 457–466.CrossRefGoogle Scholar
  26. 26.
    Nottrott, S., Hartmuth, K., Fabrizio, P., Urlaub, H., Vidovic, I., Ficner, R., et al. (1999). Functional interaction of a novel 15.5kD [U4/U6.U5] tri-snRNP protein with the 5′ stem-loop of U4 snRNA. The EMBO Journal, 18, 6119–6133.CrossRefGoogle Scholar
  27. 27.
    Sojka, L., Fucik, V., Krasny, L., Barvik, I., & Jonak, J. (2007). YbxF, a protein associated with exponential-phase ribosomes in Bacillus subtilis. Journal of Bacteriology, 189, 4809–4814.CrossRefGoogle Scholar
  28. 28.
    Kuhn, J. F., Tran, E. J., & Maxwell, E. S. (2002). Archaeal ribosomal protein L7 is a functional homolog of the eukaryotic 15.5kD/Snu13p snoRNP core protein. Nucleic Acids Research, 30, 931–941.CrossRefGoogle Scholar
  29. 29.
    Rozhdestvensky, T. S., Tang, T. H., Tchirkova, I. V., Brosius, J., Bachellerie, J.-P., & Hüttenhofer, A. (2003). Binding of L7Ae protein to the K-turn of archaeal snoRNAs: A shared RNA binding motif for C/D and H/ACA box snoRNAs in Archaea. Nucleic Acids Research, 31, 869–877.CrossRefGoogle Scholar
  30. 30.
    Klein, D. J., Schmeing, T. M., Moore, P. B., & Steitz, T. A. (2001). The kink-turn: A new RNA secondary structure motif. The EMBO Journal, 20, 4214–4221.CrossRefGoogle Scholar
  31. 31.
    Watkins, N. J., Dickmanns, A., & Luhrmann, R. (2002). Conserved stem II of the box C/D motif is essential for nucleolar localization and is required, along with the 15.5 K protein, for the hierarchical assembly of the box C/D snoRNP. Molecular and Cellular Biology, 22, 8342–8352.CrossRefGoogle Scholar
  32. 32.
    Marmier-Gourrier, N., Clery, A., Senty-Segault, V., Charpentier, B., Schlotter, F., Leclerc, F., et al. (2003). A structural, phylogenetic, and functional study of 15.5-kD/Snu13 protein binding on U3 small nucleolar RNA. RNA, 9, 821–838.CrossRefGoogle Scholar
  33. 33.
    Cho, I. M., Lai, L. B., Susanti, D., Mukhopadhyay, B., & Gopalan, V. (2010). Ribosomal protein L7Ae is a subunit of archaeal RNase P. Proceedings of the National Academy of Sciences of the United States of America, 107, 14573–14578.ADSCrossRefGoogle Scholar
  34. 34.
    Suryadi, J., Tran, E. J., Maxwell, E. S., & Brown, B. A. (2005). The crystal structure of the Methanocaldococcus jannaschii multifunctional L7Ae RNA-binding protein reveals an induced-fit interaction with the box C/D RNAs. Biochemistry, 44, 9657–9672.CrossRefGoogle Scholar
  35. 35.
    Xue, S., Wang, R., Yang, F., Terns, R. M., Terns, M. P., Zhang, X., et al. (2010). Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle. Molecular Cell, 39, 939–949.CrossRefGoogle Scholar
  36. 36.
    Baird, N. J., Zhang, J., Hamma, T., & Ferré-D’Amaré, A. R. (2012). YbxF and YlxQ are bacterial homologs of L7Ae, and bind K-turns but not K-loops. RNA, 18, 759–770.CrossRefGoogle Scholar
  37. 37.
    Huang, L., & Lilley, D. M. J. (2013). The molecular recognition of kink turn structure by the L7Ae class of proteins. RNA, 19, 1703–1710.CrossRefGoogle Scholar
  38. 38.
    Goody, T. A., Melcher, S. E., Norman, D. G., & Lilley, D. M. J. (2004). The kink-turn motif in RNA is dimorphic, and metal ion dependent. RNA, 10, 254–264.CrossRefGoogle Scholar
  39. 39.
    Shi, X., Huang, L., Lilley, D. M., Harbury, P. B., & Herschlag, D. (2016). The solution structural ensembles of RNA kink-turn motifs and their protein complexes. Nature Chemical Biology, 12, 146–152.CrossRefGoogle Scholar
  40. 40.
    Turner, B., & Lilley, D. M. J. (2008). The importance of G.A hydrogen bonding in the metal ion- and protein-induced folding of a kink turn RNA. J Molec Biol, 381, 431–442.CrossRefGoogle Scholar
  41. 41.
    Tsai, C. J., Ma, B., Sham, Y. Y., Kumar, S., & Nussinov, R. (2001). Structured disorder and conformational selection. Proteins, 44, 418–427.CrossRefGoogle Scholar
  42. 42.
    Koshland, D. E. (1958). Application of a theory of enzyme specificity to protein synthesis. Proceedings of the National Academy of Sciences of the United States of America, 44, 98–104.ADSCrossRefGoogle Scholar
  43. 43.
    Pitici, F., Beveridge, D. L., & Baranger, A. M. (2002). Molecular dynamics simulation studies of induced fit and conformational capture in U1A-RNA binding: Do molecular substates code for specificity? Biopolymers, 65, 424–435.CrossRefGoogle Scholar
  44. 44.
    Okazaki, K., & Takada, S. (2008). Dynamic energy landscape view of coupled binding and protein conformational change: Induced-fit versus population-shift mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 105, 11182–11187.ADSCrossRefGoogle Scholar
  45. 45.
    Weikl, T. R., & von Deuster, C. (2008). Selected-fit versus induced-fit protein binding: Kinetic differences and mutational analysis. Proteins, 75, 104–110.CrossRefGoogle Scholar
  46. 46.
    Hammes, G. G., Chang, Y. C., & Oas, T. G. (2009). Conformational selection or induced fit: A flux description of reaction mechanism. Proceedings of the National Academy of Sciences of the United States of America, 106, 13737–13741.ADSCrossRefGoogle Scholar
  47. 47.
    Csermely, P., Palotai, R., & Nussinov, R. (2010). Induced fit, conformational selection and independent dynamic segments: An extended view of binding events. Trends in Biochemical Sciences, 35, 539–546.CrossRefGoogle Scholar
  48. 48.
    Zhou, H. X. (2010). From induced fit to conformational selection: A continuum of binding mechanism controlled by the timescale of conformational transitions. Biophysical Journal, 98, L1517.Google Scholar
  49. 49.
    Wang, J., Fessl, T., Schroeder, K. T., Ouellet, J., Liu, Y., Freeman, A. D., et al. (2012). Single-molecule observation of the induction of k-turn RNA structure on binding L7Ae protein. Biophys J, 103, 2541–2548.CrossRefGoogle Scholar
  50. 50.
    He, C. (2010). Grand challenge commentary: RNA epigenetics? Nature Chemical Biology, 6, 863–865.CrossRefGoogle Scholar
  51. 51.
    Cantara, W. A., Crain, P. F., Rozenski, J., McCloskey, J. A., Harris, K. A., Zhang, X., et al. (2011). The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Research, 39, D195–D201.CrossRefGoogle Scholar
  52. 52.
    Schibler, U., Kelley, D. E., & Perry, R. P. (1977). Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. Journal of Molecular Biology, 115, 695–714.CrossRefGoogle Scholar
  53. 53.
    Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., et al. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485, 201–206.ADSCrossRefGoogle Scholar
  54. 54.
    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.CrossRefGoogle Scholar
  55. 55.
    Huang, L., Ashraf, S., Wang, J., & Lilley, D. M. (2017). Control of box C/D snoRNP assembly by N6-methylation of adenine. EMBO Reports, 18, 1631–1645. Scholar
  56. 56.
    Kiss-Laszlo, Z., Henry, Y., Bachellerie, J. P., Caizergues-Ferrer, M., & Kiss, T. (1996). Site-specific ribose methylation of preribosomal RNA: A novel function for small nucleolar RNAs. Cell, 85, 1077–1088.CrossRefGoogle Scholar
  57. 57.
    Tycowski, K. T., Smith, C. M., Shu, M. D., & Steitz, J. A. (1996). A small nucleolar RNA requirement for site-specific ribose methylation of rRNA in Xenopus. Proceedings of the National Academy of Sciences of the United States of America, 93, 14480–14485.ADSCrossRefGoogle Scholar
  58. 58.
    Tran, E. J., Zhang, X., & Maxwell, E. S. (2003). Efficient RNA 2′-O-methylation requires juxtaposed and symmetrically assembled archaeal box C/D and C′/D′ RNPs. The EMBO Journal, 22, 3930–3940.CrossRefGoogle Scholar
  59. 59.
    Bleichert, F., Gagnon, K. T., Brown, B. A., Maxwell, E. S., Leschziner, A. E., Unger, V. M., et al. (2009). A dimeric structure for archaeal box C/D small ribonucleoproteins. Science, 325, 1384–1387.ADSCrossRefGoogle Scholar
  60. 60.
    Ye, K., Jia, R., Lin, J., Ju, M., Peng, J., Xu, A., et al. (2009). Structural organization of box C/D RNA-guided RNA methyltransferase. Proceedings of the National Academy of Sciences of the United States of America, 106, 13808–13813.ADSCrossRefGoogle Scholar
  61. 61.
    Lin, J., Lai, S., Jia, R., Xu, A., Zhang, L., Lu, J., et al. (2011). Structural basis for site-specific ribose methylation by box C/D RNA protein complexes. Nature, 469, 559–563.ADSCrossRefGoogle Scholar
  62. 62.
    Watkins, N. J., Newman, D. R., Kuhn, J. F., & Maxwell, E. S. (1998). In vitro assembly of the mouse U14 snoRNP core complex and identification of a 65-kDa box C/D-binding protein. RNA, 4, 582–593.CrossRefGoogle Scholar
  63. 63.
    Omer, A. D., Ziesche, S., Ebhardt, H., & Dennis, P. P. (2002). In vitro reconstitution and activity of a C/D box methylation guide ribonucleoprotein complex. Proceedings of the National Academy of Sciences of the United States of America, 99, 5289–5294.ADSCrossRefGoogle Scholar
  64. 64.
    Schultz, A., Nottrott, S., Watkins, N. J., & Luhrmann, R. (2006). Protein-protein and protein-RNA contacts both contribute to the 15.5 K-mediated assembly of the U4/U6 snRNP and the box C/D snoRNPs. Molecular and Cellular Biology, 26, 5146–5154.CrossRefGoogle Scholar
  65. 65.
    McKeegan, K. S., Debieux, C. M., Boulon, S., Bertrand, E., & Watkins, N. J. (2007). A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP assembly. Molec Cell Biol, 27, 6782–6793.CrossRefGoogle Scholar
  66. 66.
    Huang, L., & Lilley, D. M. J. (2013). The molecular recognition of kink-turn structure by the L7Ae class of proteins. RNA, 19, 1703–1710.CrossRefGoogle Scholar
  67. 67.
    Szewczak, L. B., DeGregorio, S. J., Strobel, S. A., & Steitz, J. A. (2002). Exclusive interaction of the 15.5 kD protein with the terminal box C/D motif of a methylation guide snoRNP. Chemistry and Biology, 9, 1095–1107.CrossRefGoogle Scholar
  68. 68.
    Caffarelli, E., Fatica, A., Prislei, S., De Gregorio, E., Fragapane, P., & Bozzoni, I. (1996). Processing of the intron-encoded U16 and U18 snoRNAs: The conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA. The EMBO Journal, 15, 1121–1131.CrossRefGoogle Scholar
  69. 69.
    Huang, L., & Lilley, D. M. J. (2016). A quasi-cyclic RNA nano-scale molecular object constructed using kink turns. Nanoscale, 8, 15189–15195.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB ComplexThe University of DundeeDundeeUK

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