1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics

Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing

  1. Eric Hoffer
  2. Samuel Hong
  3. S. Sunita
  4. Tatsuya Maehigashi
  5. Ruben L Gonzalez Jnr
  6. Paul Whitford
  7. Christine M Dunham  Is a corresponding author
  1. Emory University School of Medicine, United States
  2. Columbia University, United States
  3. Northeastern University, United States
https://doi.org/10.7554/eLife.51898
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  1. Eric Hoffer
  2. Samuel Hong
  3. S. Sunita
  4. Tatsuya Maehigashi
  5. Ruben L Gonzalez Jnr
  6. Paul Whitford
  7. Christine M Dunham
(2020)
Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing
eLife 9:e51898.
https://doi.org/10.7554/eLife.51898
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Abstract

Modifications in the tRNA anticodon loop, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguaonosine modification at guanine nucleotide 37 (m1G37) located in the anticodon loop, immediately adjacent to the anticodon nucleotides 34-36. The absence of m1G37 in tRNAPro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNAPro bound to either cognate or slippery codons to determine how the m1G37 modification prevents mRNA frameshifting. The structures reveal that certain codon-anticodon contexts and m1G37 destabilize interactions of tRNAPro with the peptidyl site, causing large conformational changes typically only seen during EF-G mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how m1G37 stabilizes the interactions of tRNAPro with the ribosome and the influence of slippery codons on the mRNA reading frame.

Data availability

Crystallography, atomic coordinates, and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB codes 6NTA, 6NSH, 6NUO, 6NWY, 6O3M, 6OSI)

The following data sets were generated

Article and author information

Author details

  1. Eric Hoffer

    Biochemistry, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Samuel Hong

    Biochemistry, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. S. Sunita

    Biochemistry, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Tatsuya Maehigashi

    Biochemistry, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Ruben L Gonzalez Jnr

    Department of Chemistry, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1344-5581

  6. Paul Whitford

    Physics, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Christine M Dunham

    Biochemistry, Emory University School of Medicine, Atlanta, United States
    For correspondence
    cmdunha@emory.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8821-688X

Funding

National Institutes of Health (R01GM093278)

  • Christine M Dunham

National Institutes of Health (R01GM119386)

  • Ruben L Gonzalez

National Science Foundation (MCB-1915843)

  • Paul Whitford

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Hoffer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Eric Hoffer
  2. Samuel Hong
  3. S. Sunita
  4. Tatsuya Maehigashi
  5. Ruben L Gonzalez Jnr
  6. Paul Whitford
  7. Christine M Dunham
(2020)
Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing
eLife 9:e51898.
https://doi.org/10.7554/eLife.51898

Share this article

https://doi.org/10.7554/eLife.51898

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