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Chapter 6 : Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach

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Abstract:

This chapter focuses on the structural implications resulting from the occurrence of this residue in tRNA and also presents an overview of the tRNA pseudouridylation sites. The principle of molecular dynamics (MD) resides in the numerical integration of the Newtonian equations of motion. The potential energy function contains several terms that account for covalent bond stretching, bond angle bending, harmonic dihedral bending, and nonbonded interactions including van der Waals and Coulombic terms. The residence time of this water molecule, which is consistently observed in several MD simulations, was estimated to be significantly longer than 500 ps. This water molecule forms an important structural link between the nucleotide backbone and the modified base and, thus, reduces the conformational mobility of the RNA close to the pseudouridylation site. Summarizing the preceding information suggests strongly that the main function of pseudouridylation close to the anticodon is to stabilize the structure of the loop by reducing its intrinsic dynamics, likely to avoid codon misreading. Pseudouridines are also important in ribosomal RNA and small nuclear RNA. It would not be surprising that in most structural contexts pseudouridines would stabilize rRNA and snRNA in a similar manner as in tRNA. In snRNA, the occurrence of pseudouridines in single-stranded regions may be required to improve their recognition features. Recent MD studies on the conformational behavior of 2'-OH groups in tRNA may be considered as a first approach toward the investigation of the roles of 2'-O-methyl groups.

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6

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Figures

Image of Figure 1
Figure 1

Secondary structure of the yeast tRNA anticodon hairpin.

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6
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Image of Figure 2
Figure 2

Locations and frequencies of tRNA pseudouridylation sites extracted from the tRNA database containing 546 tRNA sequences ( ). Sites for which more than 10 modifications have been counted are surrounded by a bold circle. The letters A, Β and Ε refer to the three kingdoms (A, archaea [59 sequences]; B, eubacteria [133 sequences], and E, eukaryotes [212 sequences], while Ο includes the remaining 142 mitochondrial, chloroplastic and viroid tRNA sequences. The black square marks modifications occurring in all four (Α, Β, Ε and O) subdomains; the (not Α), (not B) and ε (not E) symbols mark modifications occurring respectively in the (Β, Ε, Ο), (A, E, O), and (A, B, O) subdomains. For the tRNA numbering, see and Appendix 5. The asterisk indicates that the sequence of minor tRNA containing the rare ΨΑΨanticodon ( ) has been added to the present compilation.

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6
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Image of Figure 3
Figure 3

(Top) Snapshot extracted from a 500-ps MD simulation of the solvated yeast tRNA anticodon hairpin. This snapshot shows the water molecule linking the base of Ψ to its nucleotide backbone through a N-H...O and two O-H...O hydrogen bonds (O = pro-R). This water molecule is stable for at least 500 ps and contributes to reduce the mobility of base 32 ( ). This reduced conformational mobility results in the stabilization of the single bifurcated (Ψ)O...Ν(C) interaction specific of the 32-38 "pseudo-base pair". (Bottom) Typical time course of the (Ψ)O...Ν(C) distance extracted from a 500-ps MD simulation of the solvated yeast tRNAAsp anticodon hairpin ( ).

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6
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Image of Figure 4
Figure 4

Substitution of a pyrimidine at position 35 of the anticodon loop by a pseudouridine. (Left) The occurrence of a (U)C-H...O,(U) hydrogen bond is inferred from the refined crystal structure of yeast tRNAAsp (Westhof et al., 1985). This interaction is analogous to the (A)N...H-O,(U) hydrogen bond found in the crystal structure of tRNAPhe ( ). This C-H...O interaction displays a stable dynamical behavior in several MD simulations of the tRNAAsp anticodon hairpin ( ). (Right) Substitution of a pyrimidine at position 35 by a pseudouridine increases the strength of the interaction established between base 35 and the ribose hydroxyl group of base 33, since a C-H...O contact is replaced by an N-H...O bond

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6
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Figure 5

Substitution for a pyrimidine at position 36 of the anticodon loop by a pseudouridine. (Left) A (C)C-H...O(U) interaction is present in the crystal structure of yeast tRNAAsp ( ). This interaction is maintained in several 500-ps MD simulations of the anticodon hairpin ( ). Additionally, U, is stabilized by the strong (U)N-H...O(C) internucleotide hydrogen bond and the weaker (U)C-H...O′ intranucleotide C-H...O interaction. The base of C is similarly linked to its backbone through a C Η...O′ hydrogen bond. U is thus linked to C through an array of strong N-H...O and weaker C-H...O hydrogen bonds. (Right) A replacement of a pyrimidine at position 36 by a pseudouridine would not perturb the array of existing hydrogen bonds at positions 33 and 36. Instead, it results in a strengthening of the interaction established between the two bases through the replacement of the C-H...O interaction by an N-H...O hydrogen bond.

Citation: Auffinger P, Westhof E. 1998. Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach, p 103-112. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch6
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References

/content/book/10.1128/9781555818296.chap6
1. Agris, P. F. 1996. The importance of being modified: roles of modified nucleosides and Mg2+ in RNA structure and function. Prog. Nucleic Acid Res. Mol. Biol. 53:79129.
2. Arnez, J. G.,, and T. A. Steitz. 1994. Crystal structure of unmodified tRNAGln complexed with glutaminyl-tRNA synthetase and ATP suggests a possible role for pseudo-uridines in stabilization of RNA structure. Biochemistry 33:75607567.
3. Arnez, J. G.,, and T. A. Steitz. 1996. Crystal structure of three mysacylating mutants of Escherichia coli glutaminyl-tRNA synthetase complexed with tRNAGln and ATP. Biochemistry 35: 1472514733.
4. Auffinger, P.,, S. Louise-May,, and E. Westhof. 1996a. Hydration of C-H groups in tRNA. Faraday Discuss. 103:151174.
5. Auffinger, P.,, S. Louise-May,, and E. Westhof. 1996b. Molecular dynamics simulations of the anticodon hairpin of tRNAAsp: structuring effects of C-H...O hydrogen bonds and of long-range hydration forces. J. Am. Chem. Soc. 118:11811189.
6. Auffinger, P.,, and E. Westhof. 1996. H-bond stability in the tRNAAsp anticodon hairpin: 3 ns of multiple molecular dynamics simulations. Biophys. J. 71:940954.
7. Auffinger, P.,, and E. Westhof. 1997a. RNA hydration: three nanoseconds of multiple molecular dynamics simulations of the solvated tRNAAsp anticodon hairpin. J. Mol. Biol. 269: 326341.
8. Auffinger, P.,, and E. Westhof. 1997b. Rules governing the orientation of the 2'-hydroxyl group in RNA. J. Mol. Biol. 274: 5463.
9. Auffinger, P.,, and E. Westhof,. 1998a. Molecular dynamics of nucleic acids. In P. V. R. Schleyer (ed.), Encyclopedia of Computational Chemistry, in press. John Wiley &C Sons, New York, N.Y..
10. Auffinger, P.,, and E. Westhof. 1998b. Simulations of the molecular dynamics of nucleic acids. Curr. Opin. Struct. Biol., in press.
11. Bare, L. A.,, and O. C. Uhlenbeck. 1986. Specific substitution into the anticodon loop of yeast tyrosine transfer RNA. Biochemistry 25:58255830.
12. Brooks, C. L.,, M. Karplus,, and B. M. Pettitt. 1988. Proteins: a theoretical perspective of dynamics, structure and thermodynamics, vol. LXX1. John Wiley & Sons, New York, N.Y..
13. Cheatham, T. E.,, and P. A. Kollman. 1997. Molecular dynamics simulations can reasonably represent the structural differences in DNA:DNA and RNA:RNA and DNA:RNA hybrid duplexes. J. Am. Chem. Soc. 119:48054194.
14. Claesson, C.,, F. Lustig,, T. Boren,, C. Simonsson,, M. Barciszewska,, and U. Lagerkvist. 1995. Glycine codon discrimination and the nucleotide in position 32 of the anticodon loop. J. Mol. Biol. 247:191196.
15. Cornell, W. D.,, P. Cieplak,, C. I. Bayly,, I. R. Gould,, K. M. Merz,, D. M. Ferguson,, D. C. Spellmeyer,, T. Fox,, J. W. Caldwell,, and P. A. Kollman. 1995. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 117:51795197.
16. Davis, D. R. 1995. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res. 23:50205026.
17. Davis, D. R.,, and C. D. Poulter. 1991. 1H-15N NMR studies of Escherichia coli tRNAPhe from hisT mutants: a structural role for pseudouridine. Biochemistry 30:42234231.
18. Desiraju, G. R. 1996. The C-H...O hydrogen bond: structural implications and supramolecular design. Acc. Chem. Res. 29: 441449.
19. Dirheimer, G.,, W. Baranowski,, and G. Keith. 1995. Variations in tRNA modifications, particularly of their queunine content in higher eukaryotes. Its relation to malignancy grading. Biochimie 77:99103.
20. Durant, P. C.,, and D. R. Davis. 1997. The effect of pseudouridine and pH on the structure and dynamics of the anticodon stem-loop of tRNALys,3. Nucleic Acids Symp. Ser. 36:5657.
21. Griffey, R. H.,, D. Davis,, Z. Yamaizumi,, S. Nishimura,, A. Bax,, B. Hawkins,, and C. D. Poulter. 1985. 15N-labeled Escherichia coli tRNA,Met, tRNAGln, tRNATyr, and tRNAPhc. Double resonance and two dimensional NMR of Nl-labeled pseudouridine.J. Biol. Chem. 260:97349741.
22. Grosjean, H.,, Z. Szweykowska-Kulinska,, Y. Motorin,, F. Fasiolo,, and G. Simos. 1997. Intron-dependent enzymatic formation of modified nucleosides in eukaryotic tRNAs: a review. Biochimie 79:293302.
23. Hall, K. B.,, and L. W. McLaughlin. 1991. Properties of a U1/ mRNA 5' splice site duplex containing pseudouridines as measured by thermodynamics and NMR methods. Biochemistry 30:17951801.
24. Hall, K. B.,, and L. W. McLauglin. 1992. Properties of pseudouridine Nl imino protons located in the major groove of an A-form RNA duplex. Nucleic Acids Res. 20:18831889.
25. Hermann, T.,, P. Auffinger,, W. G. Scott,, and E. Westhof. 1997. Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme. Nucleic Acids Res. 25:34213427.
26. Hermann, T.,, P. Auffinger,, and E. Westhof. 1998. Molecular dynamics investigations on the hammerhead ribozyme RNA. Eur. J. Biophys., in press.
27. Johnson, P. F.,, and J. Abelson. 1983. The yeast tRNATyr gene intron is essential for correct modification of its tRNA product. Nature 302:681687.
28. Kolk, M. H.,, H. A. Heus,, and C. W. Hilbers. 1997. The structure of the isolated, central hairpin of the HDV antigenomic ribozyme: novel structural features and similarity of the loop in the ribozyme and free in solution. EMBO J. 16:36853692.
29. Lane, B. G.,, J. Ofengand,, and M. W. Gray. 1995. Pseudouridine and O2'-methylated nucleosides. Significance of their selective occurrence in rRNA domains that function in ribosome-catalyzed synthesis of the peptide bonds in proteins. Biochimie 77:715.
30. Louise-May, S.,, P. Auffinger,, and E. Westhof. 1996. Calculation of nucleic acid conformation. Curr. Opin. Struct. Biol. 6: 289298.
31. Lustig, F.,, T. Boren,, C. Claesson,, C. Simonsson,, M. Barciszewska,, and U. Lagerkvist. 1993. The nucleotide at position 32 of the tRNA anticodon loop determines ability of anticodon UCC to discriminate among glycine codons. Proc. Natl. Acad. Sci. USA 90:33433347.
32. MacKerell, A. D.,, J. Wiorkiewicz-Kuczera,, and M. Karplus. 1995. An all-atom empirical energy function for the simulation of nucleic acids. J. Am. Chem. Soc. 117:1194611975.
33. McCammon, J. A.,, and S. C. Harvey. 1987. Dynamics of Proteins and Nucleic Acids. Cambridge University Press, New York, N.Y..
34. Miller, J.,, and P. A. Kollman. 1997. Theoretical studies of an exceptionally stable RNA tetraloop: observation of convergence from an incorrect NMR structure to the correct one using unrestrained molecular dynamics. J. Mol. Biol. 270:436450.
35. Ofengand, J.,, and A. Bakin. 1997. Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archae-bacteria, mitochondria and chloroplasts. J. Mol. Biol. 266:246268.
36. Ofengand, J.,, A. Bakin,, J. Wrzesinski,, K. Nurse,, and B. G. Lane. 1995. The pseudouridine residues of ribosomal RNA. Biochem. Cell Biol. 73:915924.
37. Pearlman, D. A.,, D. A. Case,, J. W. Caldwell,, W. S. Ross,, T. E. Cheatham,, S. DeBolt,, D. Ferguson,, G. Seibel,, and P. Kollman. 1995. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comp. Phys. Commun. 91: 141.
38. Pearlman, D. A.,, D. A. Case,, J. W. Caldwell,, W. S. Ross,, T. E. Cheatham,, D. M. Ferguson,, G. L. Seibel,, U. C. Singh,, P. K. Weiner,, and P. A. Kollman. 1994. AMBER 4.1. University of California, San Francisco.
39. Pley, H. M.,, K. M. Flaherty,, and D. B. McKay. 1994. Three-dimensional structure of a hammerhead ribozyme. Nature 372: 6874.
40. Pochon, F.,, A. M. Michelson,, M. Grunberg-Manago,, W. E. Cohn,, and L. Dondon. 1964. Polynucleotide analogues. III. Polypseudouridylic acid: synthesis and some physicochemical and biochemical properties. Biochim. Biophys. Acta 80:441447.
41. Quigley, G. J.,, and A. Rich. 1976. Structural domains of transfer RNA molecules. Science 194:796806.
42. Rees, B.,, J. Cavarelli,, and D. Moras. 1996. Conformational flexibility of tRNA: structural changes in yeast tRNAAsp upon binding to aspartyl-tRNA synthetase. Biochimie 78:624631.
43. Rould, M. A.,, J. J. Perona,, and T. A. Steitz. 1991. Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase. Nature 352:213218.
44. Schultz, D. W.,, and M. Yarus. 1994a. tRNA structure and ribosomal function. I. tRNA nucleotide 27-43 mutations enhance first position wobble.J. Mol. Biol. 235:13771380.
45. Schultz, D. W.,, and M. Yarus. 1994b. tRNA structure and ribosomal function. II. Interaction between anticodon helix and other tRNA mutations.J. Mol. Biol. 235:13951405.
46. Schweisguth, D. C.,, and P. B. Moore. 1997. On the conformation of the anticodon loops of initiator and elongator methionine tRNAs. J. Mol. Biol. 267:505519.
47. Scott, W. G.,, J. T. Finch,, and A. Klug. 1995. The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage. Cell 81:9911002.
48. Senger, B.,, S. Auxiliens,, U. English,, F. Cramer,, and F. Fasiolo. 1997. The modified wobble base inosine in yeast tRNA'k' is a positive determinant for aminoacylation by isoleucyl-tRNA synthetase. Biochemistry 36:82698273.
49. Serra, M. J.,, T. W. Barnes,, K. Betschart,, M. J. Guiterrez,, K. J. Sprouse,, C. K. Riley,, L. Stewart,, and R. E. Temel. 1997. Improved parameters for the prediction of RNA hairpin stability. Biochemistry 36:48444851.
50. Serra, M. J.,, M. H. Lyttle,, T. J. Axenson,, C. A. Schadt,, and D. H. Turner. 1993. RNA hairpin loop stability depends on closing base pair. Nucleic Acids Res. 21:38453849.
51. Sprinzl, M.,, C. Horn,, M. Brown,, A. Ioudovitch,, and S. Steinberg. 1998. Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 26:148153.
52. Steiner, T. 1996. C-H...O hydrogen bonding in crystals. Cryst. Rev. 6:157.
53. Szweykowska-Kulinska, Z.,, B. Senger,, G. Keith,, F. Fasiolo,, and H. Grosjean. 1994. Intron-dependent formation of pseudouridines in the anticodon of Saccharomyces cerevisiae minor tRNA"c. EMBO J. 13:46364644.
54. van Gunsteren, W. F., 1993. Molecular dynamics and stochastic dynamics simulation: a primer, p. 336. In W. F. van Gunsteren,, P. K. Weiner,, and A. J. Wilkinson (ed.), Computer Simulation of Biomolecular Systems, vol. 2. ESCOM, Leiden, The Netherlands.
55. van Gunsteren, W. F.,, and H. J. C. Berendsen. 1990. Computer simulation of molecular dynamics: methodology, applications, and perspectives in chemistry. Angew. Chem. Int. Ed. Engl. 29: 9921023.
56. van Gunsteren, W. F.,, S. R. Billeter,, A. A. Eising,, P. H. Hiinenberger,, P. Kriiger,, A. E. Mark,, W. R. P. Scott,, and I. G. Tironi. 1996. Biomolecular simulation: the GROMOS96 manual and user guide. ETH Verlag, Zurich, Switzerland.
57. Wahl, C. M.,, and M. Sundaralingam. 1997. C-H...O hydrogen bonding in biology. Trends Biochem. Sci. 22:97102.
58. Wahl, M. C.,, S. T. Rao,, and M. Sundaralingam. 1996. The structure of r(UUCGCG) has a 5'-UU-overhang exhibiting Hoogsteen-like trans U-U base pairs. Nat. Struct. Biol. 3:2431.
59. Ward, D. C.,, and E. Reich. 1968. Conformational properties of polyformycin: a polyribonucleotide with individual residues in the syn conformation. Proc. Natl. Acad. Sci. USA 61:14941501.
60. Westhof, E.,, P. Dumas,, and D. Moras. 1985. Crystallographic refinement of yeast aspartic acid transfer RNA.J. Mol. Biol. 184: 119145.
61. Westhof, E.,, P. Dumas,, and D. Moras. 1988. Hydration of transfer RNA molecules: a crystallographic study. Biochimie 70: 145165.
62. Westhof, E.,, C. Rubin-Carrez,, and V. Fritsch,. 1995. The use of molecular dynamics simulations for modelling nucleic acids, p. 103131. In J. M. Goodfellow (ed.), Computer Modelling in Molecular Biology. VCH, New York, N.Y..
63. Zerfass, K.,, and H. Beier. 1992. Pseudouridine in the anticodon GψA of plant cytoplasmic tRNATyr is required for UAG and UAA suppression in the TMV-specific context. Nucleic Acids Res. 20:59115918.
64. Zichi, D. A. 1995. Molecular dynamics of RNA with the OPLS force field. Aqueous simulation of a hairpin containing a tetra-nucleotide loop.J. Am. Chem. Soc. 117:29572969.

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