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Cell. 2016 Jul 28;166(3):679-690. doi: 10.1016/j.cell.2016.05.070. Epub 2016 Jun 30.

Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast.

Author information

1
Departments of Genome Sciences and Medicine, University of Washington, Seattle, WA 98195, USA; Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA.
2
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA; Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA.
3
Departments of Genome Sciences and Medicine, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: fields@uw.edu.
4
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA; Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA. Electronic address: elizabeth_grayhack@urmc.rochester.edu.

Abstract

Translation elongation efficiency is largely thought of as the sum of decoding efficiencies for individual codons. Here, we find that adjacent codon pairs modulate translation efficiency. Deploying an approach in Saccharomyces cerevisiae that scored the expression of over 35,000 GFP variants in which three adjacent codons were randomized, we have identified 17 pairs of adjacent codons associated with reduced expression. For many pairs, codon order is obligatory for inhibition, implying a more complex interaction than a simple additive effect. Inhibition mediated by adjacent codons occurs during translation itself as GFP expression is restored by increased tRNA levels or by non-native tRNAs with exact-matching anticodons. Inhibition operates in endogenous genes, based on analysis of ribosome profiling data. Our findings suggest translation efficiency is modulated by an interplay between tRNAs at adjacent sites in the ribosome and that this concerted effect needs to be considered in predicting the functional consequences of codon choice.

KEYWORDS:

codon; ribosome; translation; yeast

PMID:
27374328
PMCID:
PMC4967012
DOI:
10.1016/j.cell.2016.05.070
[Indexed for MEDLINE]
Free PMC Article

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