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Updated: Aug 6, 2026
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Genome-wide Quantification of Translation in Budding Yeast by Ribosome Profiling
Published on: December 21, 2017
Structural adaptations for enhanced translation kinetics in evolved ribosomes
Tushar Raskar1,2, Alan Costello3,4, Ahmed H Badran3,4
1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, United States.
Nucleic Acids Research
|July 22, 2026
Summary
Engineered ribosomes show increased protein production through subtle 16S ribosomal RNA (rRNA) sequence changes that destabilize RNA structure. This structural malleability offers principles for designing ribosomes with enhanced translation properties.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Ribosomal RNA (rRNA) sequence dictates translation dynamics, but how modifications outside conserved regions affect kinetics and protein yield is unclear.
- Previous work engineered chimeric ribosomes with enhanced orthogonal translation activity using phage-assisted continuous evolution.
Purpose of the Study:
- To structurally characterize kinetically enhanced chimeric ribosomes.
- To investigate the relationship between 16S rRNA stability and translation efficiency.
- To establish principles for engineering ribosomes with altered translation properties.
Main Methods:
- Cryo-electron microscopy (cryo-EM) for structural characterization.
- Orthogonal ribosome phage-assisted continuous evolution (PACE) for ribosome engineering.
- Analysis of RNA structural adaptations and RNA-protein interactions.
Main Results:
- Evolved ribosomes exhibit extensive 16S rRNA structural adaptations, including mismatches at helical junctions, leading to local RNA-protein rearrangements.
- Destabilization of non-canonical base pairs and local RNA structural changes correlate with increased translational output.
- Compensatory mutations restoring base-pairing stability reduced translational activity.
Conclusions:
- Increased translational output is linked to subtle, localized destabilization of specific 16S rRNA elements.
- Ribosomal RNA exhibits significant structural malleability.
- Findings provide principles for engineering ribosomes with tunable translation properties.
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