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Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting

Author

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  • Panagiotis Poulis

    (Max Planck Institute for Multidisciplinary Sciences)

  • Anoshi Patel

    (Max Planck Institute for Multidisciplinary Sciences
    Institute for Microbiology and Genetics, Georg-August University of Göttingen)

  • Marina V. Rodnina

    (Max Planck Institute for Multidisciplinary Sciences)

  • Sarah Adio

    (Institute for Microbiology and Genetics, Georg-August University of Göttingen)

Abstract

When reading consecutive mRNA codons, ribosomes move by exactly one triplet at a time to synthesize a correct protein. Some mRNA tracks, called slippery sequences, are prone to ribosomal frameshifting, because the same tRNA can read both 0- and –1-frame codon. Using smFRET we show that during EF-G-catalyzed translocation on slippery sequences a fraction of ribosomes spontaneously switches from rapid, accurate translation to a slow, frameshifting-prone translocation mode where the movements of peptidyl- and deacylated tRNA become uncoupled. While deacylated tRNA translocates rapidly, pept-tRNA continues to fluctuate between chimeric and posttranslocation states, which slows down the re-locking of the small ribosomal subunit head domain. After rapid release of deacylated tRNA, pept-tRNA gains unconstrained access to the –1-frame triplet, resulting in slippage followed by recruitment of the –1-frame aa-tRNA into the A site. Our data show how altered choreography of tRNA and ribosome movements reduces the translation fidelity of ribosomes translocating in a slow mode.

Suggested Citation

  • Panagiotis Poulis & Anoshi Patel & Marina V. Rodnina & Sarah Adio, 2022. "Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31852-w
    DOI: 10.1038/s41467-022-31852-w
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    References listed on IDEAS

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    1. Valentyn Petrychenko & Bee-Zen Peng & Ana C. A. P. Schwarzer & Frank Peske & Marina V. Rodnina & Niels Fischer, 2021. "Structural mechanism of GTPase-powered ribosome-tRNA movement," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
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    1. Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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