title: Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast.
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.
authors.affiliation: 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.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Gamble
authors.affiliation: 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.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Brule
authors.affiliation: 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.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Dean
authors.affiliation: 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.
authors.forename: Stanley
authors.initials: S
authors.lastname: Fields
authors.affiliation: 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.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Grayhack
mesh_terms: D003062:Codon; D005800:Genes, Fungal; D014176:Protein Biosynthesis; D012331:RNA, Fungal / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D003062:Codon; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer
keywords: codon; ribosome; translation; yeast