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Specific length and structure rather than high thermodynamic stability enable regulatory mRNA stem-loops to pause translation

Author

Listed:
  • Chen Bao

    (University of Rochester)

  • Mingyi Zhu

    (University of Rochester)

  • Inna Nykonchuk

    (University of Rochester)

  • Hironao Wakabayashi

    (University of Rochester)

  • David H. Mathews

    (University of Rochester)

  • Dmitri N. Ermolenko

    (University of Rochester)

Abstract

Translating ribosomes unwind mRNA secondary structures by three basepairs each elongation cycle. Despite the ribosome helicase, certain mRNA stem-loops stimulate programmed ribosomal frameshift by inhibiting translation elongation. Here, using mutagenesis, biochemical and single-molecule experiments, we examine whether high stability of three basepairs, which are unwound by the translating ribosome, is critical for inducing ribosome pauses. We find that encountering frameshift-inducing mRNA stem-loops from the E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) hinders A-site tRNA binding and slows down ribosome translocation by 15-20 folds. By contrast, unwinding of first three basepairs adjacent to the mRNA entry channel slows down the translating ribosome by only 2-3 folds. Rather than high thermodynamic stability, specific length and structure enable regulatory mRNA stem-loops to stall translation by forming inhibitory interactions with the ribosome. Our data provide the basis for rationalizing transcriptome-wide studies of translation and searching for novel regulatory mRNA stem-loops.

Suggested Citation

  • Chen Bao & Mingyi Zhu & Inna Nykonchuk & Hironao Wakabayashi & David H. Mathews & Dmitri N. Ermolenko, 2022. "Specific length and structure rather than high thermodynamic stability enable regulatory mRNA stem-loops to pause translation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28600-5
    DOI: 10.1038/s41467-022-28600-5
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    References listed on IDEAS

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