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Protein-directed ribosomal frameshifting temporally regulates gene expression

Author

Listed:
  • Sawsan Napthine

    (University of Cambridge)

  • Roger Ling

    (University of Cambridge)

  • Leanne K. Finch

    (University of Cambridge)

  • Joshua D. Jones

    (University of Cambridge)

  • Susanne Bell

    (University of Cambridge)

  • Ian Brierley

    (University of Cambridge)

  • Andrew E. Firth

    (University of Cambridge)

Abstract

Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.

Suggested Citation

  • Sawsan Napthine & Roger Ling & Leanne K. Finch & Joshua D. Jones & Susanne Bell & Ian Brierley & Andrew E. Firth, 2017. "Protein-directed ribosomal frameshifting temporally regulates gene expression," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15582
    DOI: 10.1038/ncomms15582
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    Cited by:

    1. Chris H. Hill & Lukas Pekarek & Sawsan Napthine & Anuja Kibe & Andrew E. Firth & Stephen C. Graham & Neva Caliskan & Ian Brierley, 2021. "Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Matthias M. Zimmer & Anuja Kibe & Ulfert Rand & Lukas Pekarek & Liqing Ye & Stefan Buck & Redmond P. Smyth & Luka Cicin-Sain & Neva Caliskan, 2021. "The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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