IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31852-w.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31852-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31852-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sarah Adio & Tamara Senyushkina & Frank Peske & Niels Fischer & Wolfgang Wintermeyer & Marina V. Rodnina, 2015. "Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    2. 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.
    3. Jin Chen & Alexey Petrov & Magnus Johansson & Albert Tsai & Seán E. O’Leary & Joseph D. Puglisi, 2014. "Dynamic pathways of −1 translational frameshifting," Nature, Nature, vol. 512(7514), pages 328-332, August.
    4. Emily J. Rundlet & Mikael Holm & Magdalena Schacherl & S. Kundhavai Natchiar & Roger B. Altman & Christian M. T. Spahn & Alexander G. Myasnikov & Scott C. Blanchard, 2021. "Structural basis of early translocation events on the ribosome," Nature, Nature, vol. 595(7869), pages 741-745, July.
    5. Marina V. Rodnina & Andreas Savelsbergh & Vladimir I. Katunin & Wolfgang Wintermeyer, 1997. "Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome," Nature, Nature, vol. 385(6611), pages 37-41, January.
    6. Niels Fischer & Andrey L. Konevega & Wolfgang Wintermeyer & Marina V. Rodnina & Holger Stark, 2010. "Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy," Nature, Nature, vol. 466(7304), pages 329-333, July.
    7. Howard Gamper & Haixing Li & Isao Masuda & D. Miklos Robkis & Thomas Christian & Adam B. Conn & Gregor Blaha & E. James Petersson & Ruben L. Gonzalez & Ya-Ming Hou, 2021. "Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    8. Gabriel Demo & Howard B. Gamper & Anna B. Loveland & Isao Masuda & Christine E. Carbone & Egor Svidritskiy & Ya-Ming Hou & Andrei A. Korostelev, 2021. "Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    9. Joachim Frank & Rajendra Kumar Agrawal, 2000. "A ratchet-like inter-subunit reorganization of the ribosome during translocation," Nature, Nature, vol. 406(6793), pages 318-322, July.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Christine E. Carbone & Anna B. Loveland & Howard B. Gamper & Ya-Ming Hou & Gabriel Demo & Andrei A. Korostelev, 2021. "Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. 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.
    3. Lars V. Bock & Helmut Grubmüller, 2022. "Effects of cryo-EM cooling on structural ensembles," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. 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.
    5. Simon A. Fromm & Kate M. O’Connor & Michael Purdy & Pramod R. Bhatt & Gary Loughran & John F. Atkins & Ahmad Jomaa & Simone Mattei, 2023. "The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Do Hoon Kwon & Feng Zhang & Justin G. Fedor & Yang Suo & Seok-Yong Lee, 2022. "Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Patrick C. Hoffmann & Jan Philipp Kreysing & Iskander Khusainov & Maarten W. Tuijtel & Sonja Welsch & Martin Beck, 2022. "Structures of the eukaryotic ribosome and its translational states in situ," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    9. 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.
    10. Timo Flügel & Magdalena Schacherl & Anett Unbehaun & Birgit Schroeer & Marylena Dabrowski & Jörg Bürger & Thorsten Mielke & Thiemo Sprink & Christoph A. Diebolder & Yollete V. Guillén Schlippe & Chris, 2024. "Transient disome complex formation in native polysomes during ongoing protein synthesis captured by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Narayan Prasad Parajuli & Andrew Emmerich & Chandra Sekhar Mandava & Michael Y. Pavlov & Suparna Sanyal, 2023. "Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Savannah M. Seely & Narayan P. Parajuli & Arindam Tarafder & Xueliang Ge & Suparna Sanyal & Matthieu G. Gagnon, 2023. "Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. 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.
    14. 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.
    15. Sergio Cruz-León & Tomáš Majtner & Patrick C. Hoffmann & Jan Philipp Kreysing & Sebastian Kehl & Maarten W. Tuijtel & Stefan L. Schaefer & Katharina Geißler & Martin Beck & Beata Turoňová & Gerhard Hu, 2024. "High-confidence 3D template matching for cryo-electron tomography," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31852-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.