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  • Review Article
  • Published:

Viral RNA pseudoknots: versatile motifs in gene expression and replication

Nature Reviews Microbiology volume 5, pages 598–610 (2007)Cite this article

Key Points

  • RNA pseudoknots are structural motifs in RNA that are increasingly recognized in viral and cellular RNAs. They have been shown to have a various roles in virus and cellular gene expression.

  • Pseudoknots are formed upon base pairing of a single-stranded region of RNA in the loop of a hairpin to a stretch of complementary nucleotides elsewhere in the RNA chain. This simple folding strategy can generate a large number of stable three-dimensional folds, which display a diverse range of highly specific functions.

  • Pseudoknot function is frequently associated with interactions with ribosomes. The inclusion of pseudoknots in an mRNA can thus confer unusual translational properties.

  • Many RNA viruses use pseudoknots in the control of viral RNA translation, replication and the switch between the two processes. Some satellite viruses encode ribozymes with active sites that are folded by a pseudoknot.

  • In cellular RNAs, pseudoknots are associated with all aspects of mRNA function and also ribosome function, as ribosomal RNAs contain numerous pseudoknots. Other essential cellular pseudoknots have been described in telomerase RNA and transfer messenger RNA.

  • Future research into pseudoknots will focus on structure–function relationships and bioinformatics identification of pseudoknots in genomes. The use of pseudoknots in antiviral applications could also become more widespread.

Abstract

RNA pseudoknots are structural elements found in almost all classes of RNA. First recognized in the genomes of plant viruses, they are now established as a widespread motif with diverse functions in various biological processes. This Review focuses on viral pseudoknots and their role in virus gene expression and genome replication. Although emphasis is placed on those well defined pseudoknots that are involved in unusual mechanisms of viral translational initiation and elongation, the broader roles of pseudoknots are also discussed, including comparisons with relevant cellular counterparts. The relationship between RNA pseudoknot structure and function is also addressed.

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Figure 1: RNA pseudoknots in virus gene expression.
Figure 2: RNA pseudoknot structure.
Figure 3: Pseudoknots and internal ribosome entry.
Figure 4: Pseudoknots and ribosomal frameshifting.
Figure 5: Pseudoknots and transfer RNA-like structures.

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Acknowledgements

We are grateful to Stephen Smerdon for critical reading of the manuscript.

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Authors and Affiliations

  1. Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, Cambridge, UK

    Ian Brierley

  2. Division of Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Simon Pennell

  3. Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Robert J. C. Gilbert

Authors
  1. Ian Brierley
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  2. Simon Pennell
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Supplementary information

Supplementary information S1(Table)

Viral pseudoknots (PDF 111 kb)

Supplementary information S2(Table)

Cellular pseudoknots (PDF 113 kb)

Supplementary information S3(Figure)

Pseudoknot-ribosome interactions. (PDF 487 kb)

Supplementary information S4(Figure)

The hepatitis delta virus ribozyme. (PDF 230 kb)

Supplementary information S5(Figure)

The human telomerase RNA pseudoknot. (PDF 173 kb)

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Glossary

Satellite virus

A subviral agent composed of an RNA or DNA molecule that is replicated in association with a helper virus, but encapsidated in its own encoded capsid protein.

Peptidyl (P) site

The site on the small ribosomal subunit that holds the tRNA molecule that is linked to the growing end of the polypeptide chain.

Aminoacyl (A) site

The site on the small ribosomal subunit that accepts and proofreads incoming aminoacyl tRNAs prior to peptidyl transfer.

Exit (E) site

The site on the small ribosomal subunit through which tRNAs pass after they have donated their amino acid to the growing polypeptide chain.

Ribozyme

An enzyme that has an RNA as it catalytic component.

ShineDalgarno sequence

(AGGAGG). This sequence is located 5′ of the AUG codon on bacterial mRNAs and functions as the signal for the initiation of protein synthesis.

Transfer messenger RNA

(tmRNA). An RNA that possesses both tRNA and mRNA characteristics that functions in the recognition and rescue of ribosomes stalled on aberrant mRNAs, the disposal of the causative defective mRNAs and the promotion of the degradation of ribosome-associated protein fragments.

Rolling-circle replication

A mode of replication that uses a circular molecule as a template to produce concatemers of linear molecules.

Riboswitch

A conformational switch in an RNA molecule that is induced by a small metabolite, and that leads to a switch in gene-regulatory function.

Aptamer

An RNA domain, either engineered or natural, that forms a precise 3D structure and selectively binds a target molecule.

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Brierley, I., Pennell, S. & Gilbert, R. Viral RNA pseudoknots: versatile motifs in gene expression and replication. Nat Rev Microbiol 5, 598–610 (2007). https://doi.org/10.1038/nrmicro1704

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