RNA Tertiary Structure Prediction: Computational Techniques

François Major, Université de Montréal, Montréal, Canada
Patrick Gendron, Université de Montréal, Montréal, Canada

Published online: September 2005

DOI: 10.1038/npg.els.0005275

Ribonucleic acid (RNA) tertiary structure prediction is an activity that consists of inferring complete sets of atomic coordinates of RNAs, in Euclidean space, on the basis of observation, knowledge or construct. The principal goal of prediction is to obtain precise RNA tertiary structures and, thus, to reduce the costs of the discovery process by offering to scientists new possibilities to design efficient pinpoint experiments to decipher RNA function.

Keywords: prediction; structural graph; search space; algorithm; inference

Figure 1. Yeast tRNAPhe anticodon stem–loop. Cylinders are drawn between covalently bonded atoms. Hydrogen atoms are not shown. (a) 3D X-ray crystal structure. The stem is shown in blue. The U-turn motif is shown in yellow. (b) Secondary structure using a newly proposed annotation by Leontis and Westhof. Regular font indicates C3¢_endo puckers, italic font indicates C2¢_exo pucker and all nucleotides have antiglycosyl torsions.
Figure 2. Secondary structure elements. The black regions correspond to double-helical stems.
Figure 3. RNase P RNA from Haas and co-workers. (a) Secondary structure. Straight lines indicate cis Watson–Crick base pairs. Dots represent GU wobble base pairs. Arrows indicate tertiary base pairs revealed by cross-linking data. (b) Stereoview of the tertiary structure.
Figure 4. Lead-activated ribozyme. (a) Secondary structure. The symbols defined in Figure 1b were used. The empty circle indicates a trans Watson–Crick base pair. The filled circle followed by the filled box indicates a cis base pair with Watson–Crick and Hoogsteen interacting edges. The single filled circle indicates a GU wobble base pair. The arrow indicates the cleavage site. (b) Stereoview of the tertiary structure. The stems flanking the internal loop are shown in gray. The nucleotides in the internal loop are colored: C6 in red, G7 and A8 in green, and G20, A21 and G22 in yellow.
Figure 5. Catalytic core of the hairpin ribozyme. (a) Secondary structure. The symbols defined in Figure 1b were used. The empty square followed by the arrow indicates a trans base pair with Hoogsteen and sugar interacting edges. The curved arrow indicates a direction change in the backbone. (b) Stereoview of the tertiary structure. A8–A10 are shown in blue, A24–A26 are shown in green and B5–B7 (substrate) are shown in red. G+1 (substrate), A9 and C25 form a base triple.
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 References
    Gendron P, Lemieux and Major F (2001) Quantitative analysis of nucleic acid three-dimensional structures. Journal of Molecular Biology 308(5): 919–936.
    Haas ES, Brown JW, Pitulle C and Pace NR (1994) Further perspective on the catalytic core and secondary structure of ribonuclease P RNA. Proceedings of the National Academy of Sciences of the United States of America 91: 2527–2531.
    Leontis NB and Westhof E (1998) Conserved geometrical base-pairing patterns in RNA. Quarterly Reviews of Biophysics 31: 399.
    book Major F, Lemieux S and Ftouhi M (1998) "Computer RNA three-dimensional modeling from low-resolution data and multiple-sequence information". In: Leontis NB and Santa Lucia J (eds.) Molecular Modeling of Nucleic Acids, pp. 394–404. Washington, DC: American Chemical Society Books.
    Major F, Turcotte M, Gautheret D, et al. (1991) The combination of symbolic and numerical computation for three-dimensional modeling of RNA. Science 253(5025): 1255–1260.
    Malhotra A, Tan RK and Harvey SC (1994) Modeling large RNAs and ribonucleoprotein particles using molecular mechanics techniques. Biophysical Journal 66: 1777.
    Massire C, Jaeger L and Westhof E (1998) Derivation of the three-dimensional architecture of bacterial ribonuclease P RNAs from comparative sequence analysis. Journal of Molecular Biology 279(4): 773–793.
    Pinard R, Hampel K, Heckman JE, et al. (2001) Functional involvement of G8 in the hairpin ribozyme cleavage mechanism. EMBO Journal 20(22): 6434–6442.
    Rivas E and Eddy SR (1999) A dynamic programming algorithm for RNA structure prediction including pseudoknots. Journal of Molecular Biology 285: 2053–2068.
    book Saenger W (1984) Principles of Nucleic Acid Structure. New York, NY: Springer-Verlag.
    book Zuker M, Mathews DH and Turner DH (1999) "Algorithms and thermodynamics for RNA secondary structure prediction: a practical guide". In: Barciszewski and Clark BFC (eds.) RNA Biochemistry and Biotechnology. NATO ASI Series. Dorchrecht: Kluwer Academic Publishers.
 Further Reading
    book Cedergren RJ and Major F (1998) "Modeling the tertiary structure of RNA". In: Simons RW and Grunberg-Manago M (eds.) RNA Structure and Function. New York, NY: Cold Spring Harbor Laboratory Press.
    Lemieux S, Chartrand P, Cedergen R and Major F (1998) Modeling active RNA structures using the intersection of conformational space: application to the lead-activated ribozyme. RNA 4: 739–749.
    Major F, Turcotte M, Gautheret D, et al. (1991) The combination of symbolic and numerical computation for three-dimensional modeling of RNA. Science 253: 1255.
    book Michel F and Costa M (1998) "Inferring RNA structure by phylogenetic and genetic analyses". In: Simons RW and Grunberg-Manago M (eds.) RNA Structure and Function. New York, NY: Cold Spring Harbor Laboratory Press.
    Michel F, Costa M, Massire C and Westhof E (2000) Modelling RNA tertiary structure from patterns of sequence variation. Methods in Enzymology 317: 491.
    Mueller F and Brimacombe R (1997) A new model for the three-dimensional folding of E. coli 16S ribosomal RNA: I. Fitting the RNA to a 3D electron microscopic map at 20 angstroms. Journal of Molecular Biology 271: 524.
 Web Links
    ePath Protein Data Bank. A database that contains three-dimensional coordinates of proteins, DNA and RNA structures, as determined mainly by experimental, but also theoretical methods http://www.rcsb.org/

Related Sub-Topics:

Nucleic Acid Structure | RNA Structure and Function | Techniques and Tools in Molecular Biology | Computational Molecular Biology | Nucleic Acids: Structure, Function, Metabolism
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Article Title: RNA Tertiary Structure Prediction: Computational Techniques
 
How to Cite close
Major, François, and Gendron, Patrick(Sep 2005) RNA Tertiary Structure Prediction: Computational Techniques. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005275]