Abstract
Here I present a three-dimensional model of a novel element of RNA tertiary structure. A common loop motif composed of adjacent, sheared G·A and A·N non-canonical base pairs is proposed to form long-range tertiary interactions with other RNA residues. The widespread distribution of this G·A/A·N docking module suggests that the putative long-range docking interaction plays an important role in specifying the tertiary structure of large RNAs, and perhaps the quaternary structure of some intermolecular RNA–RNA interactions. Application of this docking module hypothesis to the hammerhead ribozyme provides crucial constraints for the calculation of three-dimensional models of its self-cleaving conformation.
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References
Chastain, M. & Tinoco, I., Jr., Structural elements in RNA. Prog. Nucleic. Acid Res. molec. Biol. 41, 131–177 1991).
Holbrook, S.R., Sussman, J.L., Warrant, R.W. & Kim, S.-H. Crystal structure of yeast phenylalanine transfer RNA II. Structural features and functional implications. J. molec. Biol. 123, 631–660 (1978).
Jack, A., Ladner, J.E. & Klug, A. Crystallographic refinement of yeast phenylalanine transfer RNA at 2.5 Å resolution. J. molec. Biol. 108, 619–649 (1976).
Westhof, E., Dumas, P. & Moras, D. Crystallographic refinement of yeast aspartic acid transfer RNA. J. molec. Biol. 184, 119–145 (1985).
Biou, V., Yaremchuk, A., Tukalo, M. & Cusack, S. The 2.9 Å crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNASer. Science 263, 1404–1410 (1994).
Rould, M.A., Perona, J.J. & Steitz, T.A. Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase. Nature 352, 213–218 (1991).
Cavarelli, J., Rees, B., Ruff, M., Thierry, J.C. & Moras, D. Yeast tRNAAsp recognition by its cognate class II aminoacyl-tRNA synthetase. Nature 362, 181–184 (1993).
Basavappa, R. & Sigler, P. B. The 3 Å crystal structure of yeast initiator tRNA: functional implications in initiator/elongator discrimination. EMBO J. 10, 3105–3111 (1991).
Varani, G., Cheong, C. & Tinoco, I., Jr. Structure of an unusually stable RNA hairpin. Biochemistry. 30, 3280–3289 (1991).
Heus, H. & Pardi, A. Structural features that give rise to the unusual stability of RNA hairpins containing GNRA loops. Science 253, 191–194 (1991).
Wimberly, B., Varani, G. & Tinoco, I. Jr. The conformation of loop E of eukaryotic 5S ribosomal RNA. Biochemistry. 32, 1078–1087 (1993).
Szewczak, A.A., Moore, P.B., Chang, Y.L. & Wool, I.G. The conformation of the sarcin/ricin loop from 28S ribosomal RNA. Proc. natn. Acad. Sci. U.S.A. 90, 9581–9585 (1993).
SantaLucia, J. & Turner, D.H. Structure of (rGGC(GA)GCC)2 in solution from NMR and restrained molecular dynamics. Biochemistry. 32, 12612–12623 (1993).
Leclerc, F., Cedergren, R. & Ellington, A.D. A three-dimensional model of the Rev-binding element of HIV-I derived from analyses of aptamers. Nature struct. Biol. 1, 293–300 (1994).
Branch, A. D., Benenfeld, B. J. & Robertson, H. D. Ultraviolet light-induced crosslinking reveals a unique region of local tertiary structure in potato spindle tuber viroid and HeLa 5S RNA. Proc. natn. Acad. Sci. U.S.A. 82, 6590–6594 (1985).
Keese, P. & Symons, R. H. Domains in viroids: evidence of intermolecular RNA rearrangements and their contribution to viroid evolution. Proc. natn. Acad. Sci. U.S.A. 82, 4582–4586 (1985).
Gutell, R. R., Larsen, N. & Woese, C. R. Lessons from an evolving rRNA: 16S and 23S rRNA structures from a comparative perspective. Microbiol. Rev. 58, 10–26 (1994).
Nierhaus, K. H., Schilling-Bartetzko, S. & Twardowski, T. The two main states of the elongating ribosome and the role of the alpha-sarcin stem-loop structure of 23S RNA. Biochimie 74, 403–410 (1992).
Wool, I.G., Gluck, A. & Endo, Y. Ribotoxin recognition of ribosomal RNA and a proposal for the mechanism of translocation. Trends biochem. Sci. 17, 266–269 (1992).
Gluck, A., Endo, Y. & Wool, I.G. The ribosomal RNA identity elements for ricin and for alpha-sarcin: mutations in the putative CG pair that closes a GAGA tetraloop. Nucleic Acids Res. 22, 321–324 (1994).
Butcher, S.E. & Burke, J.M. A photo-cross-linkable tertiary structure motif found in functionally distinct RNA molecules is essential for catalytic function of the hairpin ribozyme. Biochemistry. 33, 992–999 (1994).
Berzal-Herranz, A., Joseph, S., Chowrira, B.M., Butchet, S.E. & Burke, J.M. Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J. 12, 2567–2573 (1993).
Aagaard, C. & Douthwaite, S. Requirement for a conserved, tertiary interaction in the core of 23S ribosomal RNA. Proc. natn Acad. Sci. U.S.A. 91, 2989–2993 (1994).
Wise, J. Guides to the heart of the spliceosome. Science 262, 1978–1979 (1993).
Pyle, A.M. Ribozymes: a distinct class of metalloenzymes. Science 261, 709–714 (1993).
Bratty, J., Chartrand, P., Ferbeyre, G. & Cedergren, R. The hammerhead RNA domain, a model ribozyme. Biochim. biophys. Acta 1216, 345–359 (1993).
Pease, A.C. & Wemmer, D.E. Characterization of the secondary structure and melting of a self-cleaved RNA hammerhead domain by 1H NMR spectroscopy. Biochemistry. 29, 9039–9046 (1990).
Heus, H.A. & Pardi, A. Nuclear magnetic resonance studies of the hammerhead ribozyme domain. Secondary structure formation and magnesium ion dependence. J. molec. Biol. 217, 113–124 (1991).
Pley, H.W., Lindes, D.S., DeLuca-Flaherty, C. & McKay, D.B. Crystals of a hammerhead ribozyme. J. biol. Chem. 268, 19658–9658 (1993).
Kim, R. et.al. High-resolution crystals and preliminary X-ray diffraction studies of a catalytic RNA. Acta crystallogr. D50, 290–292 (1994).
Major, F., Turcotte, M., Gautheret, D., Lapalme, G., Fillion, E. & Cedergren, R. The combination of symbolic and numerical computation for three-dimensional modelling of RNA. Science 253, 1255–1260 (1991).
Gautheret, D., Major, F. & Cedergren, R. Modelling the three-dimensional structure of RNA using discrete nucleotide conformational sets. J. molec. Biol. 229, 1049–1064 (1993).
Brünger, A.T. X-PLOR: a system for crystallography and NMR. (New Haven, Yale University Press;) (1992).
Mei, H.Y., Kaaref, T.W. & Bruice, T.C. A computational approach to the mechanism of self-cleavage of hammerhead RNA. Proc. natn Acad Sci. U.S.A. 86, 9727–9731 (1989).
Woisard, A., Favre, A., Clivio, P. & Fourrey, J.-L. Hammerhead ribozyme tertiary folding: intrinsic photolabeling studies. J. Am. chem. Soc. 114, 10072–10074 (1992).
Fu, D.-J., Rajur, S.B. & McLaughlin, L.W. Importance of specific guanosine N7-nitrogens and purine amino groups for efficient cleavage by a hammerhead ribozyme. Biochemistry 32, 10629–10637 (1993).
Fu, D.-J. & McLaughlin, L.W. Importance of specific adenosine N7-nitrogens for efficient cleavage by a hammerhead ribozyme. A model for magnesium binding. Biochemistry 31, 10941–10949 (1992).
Dahm, S.C., Derrick, W.B. & Uhlenbeck, O.C. Evidence for the role of solvated metal hydroxide in the hammerhead cleavage mechanism. Biochemistry 32, 13040–13045 (1993).
Ruffner, D.E. & Uhlenbeck, O.C. Thiophosphate interference experiments locate phosphates important for the hammerhead RNA self-cleavage reaction. Nucleic Acids Res, 18, 6025–6029 (1990).
Slim, G. & Gait, M.J. Configurationally defined phosphorothioate-containing oligoribonucleotides in the study of the mechanism of cleavage of hammerhead ribozymes. Nucleic. Acids Res. 19, 1183–1188 (1991).
Dahm, S.C. & Uhlenbeck, O.C. Role of divalent metal ions in the hammerhead RNA cleavage reaction. Biochemistry 30, 9464–9469 (1991).
Hertel, K.J. et al. Numbering system for the hammerhead. Nucleic Acids Res. 20, 3252 (1992).
Ruffner, D.E., Stormo, G.D. & Uhlenbeck, O.C. Sequence requirements of the hammerhead RNA self-cleavage reaction. Biochemistry 29, 10695–10702 (1990).
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Wimberly, B. A common RNA loop motif as a docking module and its function in the hammerhead ribozyme. Nat Struct Mol Biol 1, 820–827 (1994). https://doi.org/10.1038/nsb1194-820
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DOI: https://doi.org/10.1038/nsb1194-820
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