Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing
- Emory University School of Medicine, United States
- Columbia University, United States
- Northeastern University, United States
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)
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Structures of 70S bound to frameshift-prone tRNAPro6NTA, 6NSH, 6NUO, 6NWY, 6O3M, 6OSI.
Article and author information
Author details
Ruben L Gonzalez Jnr
Christine M Dunham
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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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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