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RNA Structure: Pseudoknots

  1. Alexander P Gultyaev1,
  2. René CL Olsthoorn1,
  3. Cornelis WA Pleij1,
  4. Eric Westhof2

Published Online: 17 SEP 2012

DOI: 10.1002/9780470015902.a0003134.pub2



How to Cite

Gultyaev, A. P., Olsthoorn, R. C., Pleij, C. W. and Westhof, E. 2012. RNA Structure: Pseudoknots. eLS. .

Author Information

  1. 1

    Leiden University, Leiden, Netherlands

  2. 2

    Université de Strasbourg, Strasbourg, France

Publication History

  1. Published Online: 17 SEP 2012


An RNA pseudoknot results from Watson–Crick base pairing of a single-stranded segment, located between two regions, paired to each other, with a sequence that is not located between these paired regions. This leads to a structure with at least two helical stems and two loops crossing the grooves of the helices. Pseudoknots are further stabilised by coaxial stacking between stems and the formation of triple ribonucleic acid (RNA) interactions between stems and loops. RNA pseudoknots adopt different folding topologies and are an essential part of various functional RNA molecules, including ribosomal RNAs, ribozymes and riboswitches. In this review, the thermodynamics and main structural features of pseudoknots, important for their function, are discussed: amongst others, viral tRNA-like structures, ribosomal frameshifter pseudoknots and pseudoknots formed by S-adenosylmethionine and pre-queuosine riboswitches upon binding of their respective ligands.

Key Concepts:

  • The simplest RNA pseudoknot is formed by base-pairing of nucleotides within a hairpin loop to a complementary sequence outside the hairpin (H-pseudoknot).

  • Classical H-pseudoknots consist of two coaxially stacked helical stems and two loops that cross one deep groove of one helix and the shallow groove of the other helical stem.

  • Pseudoknots are usually stabilised by coaxial stacking between stems and triple base pairs formed between the bases of the stems and loops.

  • Many complex pseudoknots may be interpreted as classical pseudoknots containing additional structural elements inserted in the pseudoknot loops.

  • Pseudoknots are folded in various types of RNA molecules and have diverse functions.

  • Limited information is available on thermodynamic stability of pseudoknots.

  • Computer-assisted prediction of pseudoknots is partially hampered by a lack of knowledge about the thermodynamics of pseudoknot folding.


  • RNA folding;
  • RNA secondary structure;
  • RNA tertiary structure;
  • ribozyme;
  • ribosome;
  • reprogramming;
  • frameshifting