RNA Structure

Abstract

Ribonucleic acid (RNA) molecules perform their function in living cells by adopting specific and highly complex 3‐dimensional structures. Like proteins, RNA structure can be described in terms of its primary (sequence), secondary (hairpins, bulges and internal loops), tertiary (A‐minor motif, 3‐way junction, pseudoknot, etc.) and quaternary structure (supermolecular organisation). Watson–Crick base pairs as well as other noncanonical base interactions are the basic building blocks of RNA secondary and tertiary structures. Metal ions are essential for the stabilisation of RNA tertiary structures and for catalytic function. In the past decade, there has been a tremendous advance in RNA structure determination, with the successful determination of the ribosome structures, as well as many other folded large RNAs. These studies have given us a unique new opportunity to understand the structure–function relationship of RNA molecules to an unprecedented level of insight.

Key Concepts:

  • Double helical tracts separated by single‐stranded nucleotides represent the basic building block of RNA structure.

  • Hairpins (or stem–loops) are the most common element of RNA secondary structure.

  • RNA secondary structure can generally be predicted successfully from sequence analysis and thermodynamic calculation.

  • RNA secondary structure is generally more stable than its tertiary structure.

  • RNA three‐dimensional structures form by joining together the different secondary structure elements through the formation of long‐range tertiary interactions.

  • Coaxial stacking between double‐stranded helices at junctions where helices come together is a major determinant of higher order RNA tertiary structure.

  • Multivalent ions are often important for thermodynamic stabilisation and catalytic activities of RNA tertiary structures.

Keywords: RNA secondary structure; RNA motifs; RNA folding; RNA tertiary structure

Figure 1.

Hierarchy of RNA folding. (a) The primary structure corresponds to the RNA sequence. (b) The secondary structure (in this case two stem–loops or hairpins) forms Watson–Crick base pairing between complementary nucleotides. (c) Tertiary interactions (coaxial stacking of double helices, long‐range tertiary interactions) lead to the final three‐dimensional structure (e.g. a pseudoknot).

Figure 2.

RNA secondary structure motifs.

Figure 3.

The secondary and tertiary structures of yeast tRNAPhe. (a) Nucleotide sequence and secondary structure of tRNAPhe represented in the classic cloverleaf fold. (b) Tertiary structure of tRNAPhe determined by X‐ray crystallography (Protein Data Bank (PDB) accession number 6tna). The corresponding stems in the secondary and tertiary structures are in the same colours.

Figure 4.

Three‐dimensional structures of RNA. Individual bases are not displayed for the 50S ribosome and group II self‐splicing intron for clarity; RNA backbones are highlighted in orange tubes. All figures are generated from PDB files using Pymol: hepatitis delta virus ribozyme (1CX0.pdb), 50S ribosome RNA (1FFK.pdb), group II intron (3IGI.pdb), hammerhead ribozyme (2GOZ.pdb), lysine riboswitch (3D0U.pdb) and ribozyme domain of group I Intron (1GID.pdb). Magnesium ions in the group I intron are highlighted with magenta spheres, whereas those in the other structures are not shown.

Figure 5.

Examples of RNA tertiary interactions. RNA backbones are highlighted as red and yellow tubes for kissing–loop, orange tubes for pseudoknot and 3‐way junction. All figures are generated from PDB files using Pymol: kissing–loop (1KIS.pdb), pseudoknot (2K95.pdb), 3‐way junction (2QUS.pdb), A‐minor motif (1FFK.pdb) and ribose zipper (1CX0.pdb). Magnesium ions which are important for stabilising 3‐way junctions and catalytic functions are highlighted with magenta spheres. Hydrogen‐bonding in the A‐minor motif and ribose zipper tertiary interactions are illustrated with dotted lines.

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Further Reading

Batey RT, Rambo RP and Doudna JA (1999) Tertiary motifs in RNA structure and folding. Angewandte Chemie (International ed. in English) 38: 2326–2343.

Blackburn GM, Gait MJ, Loakes D and Williams D (2006) Nucleic Acids in Chemistry and Biology, 2nd edn. Oxford: Oxford University Press.

Cruz JA and Westhof E (2009) The dynamic landscapes of RNA architecture. Cell 136: 604–609.

Draper DE (1996) Strategies for RNA folding. Trends in Biochemical Sciences 21: 145–149.

Nissen P, Ippolito JA, Ban N, Moore PB and Steitz TA (2001) RNA tertiary interactions in the large ribosomal subunit: the A‐minor motif. Proceedings of the National Academy of Sciences of the USA 98: 4899–4903.

Saenger W (1984) Principles of Nucleic Acids Structure. New York: Springer.

Selmer M, Dunham CM, Murphy IV FV et al. (2006) Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313: 1935–1942.

Söll D and RajBhandary UL (1995) tRNA: Structure, Biosynthesis and Function. Washington DC: ASM Press.

Tinoco IJ and Bustamante C (1999) How RNA folds. Journal of Molecular Biology 293: 271–281.

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How to Cite close
Chen, Yu, and Varani, Gabriele(Jun 2010) RNA Structure. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001339.pub2]