Coding-sequence determinants of gene expression in Escherichia coli

By Grzegorz Kudla, Andrew W. Murray, David Tollervey, Joshua B. Plotkin. Science, 2009

1,486 citations recorded by the source corpus.

Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein (GFP). When expressed in Escherichia coli, GFP protein levels varied 250-fold across the library. GFP messenger RNA (mRNA) levels, mRNA degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.

Subfields: Ecology, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/eab24268974665b979ece10d2d34c409b12ee6d7

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Citations in the corpus

Synonymous but not the same: the causes and consequences of codon bias (2010, neutral): “Kudla et al. 2009 Libraries of synthetic genes isolate the effects of synonymous mutations on gene expression.”
A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes (2010, background): “Experimental work had previously suggested that increased local mRNA stability at the translationinitiation region could prevent efficient translation initiation and hence decrease gene expression level [38,40].”
Large-scale de novo DNA synthesis: technologies and applications (2014, neutral): “89 and Quan et al.”
Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition (2016, positive): “The degeneracy of the genetic code allows multi ple codons to encode for the same amino acid (Gamow, 1954), and silent codon substitutions can influence protein expression (Ikemura, 1982; Kudla et al, 2009).”
Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line (2010, background): “Further, codon bias index does not correlate significantly with human protein abundance, in agreement with recent observations in E. coli (Kudla et al, 2009) (Table I).”
Toward a Kinetic Understanding of Eukaryotic Translation. (2018, neutral): “3) (Nackley et al. 2006; Kudla et al. 2009).”
Codon Bias as a Means to Fine-Tune Gene Expression (2015, background): “Many studies that have addressed codon bias by analyzing libraries of synthetic reporter variants have resulted mainly in the identiﬁcation of coding sequence features that affect translation initiation (Goodman et al., 2013; Kudla et al., 2009).”
DAMBE6: New Tools for Microbial Genomics, Phylogenetics, and Molecular Evolution (2017, background): “Translation initiation is often rate-limiting in bacteria and in bacteriophage (Liljenstrom and von Heijne 1987; Bulmer 1991; Xia 2007c; Xia et al. 2007; Kudla et al. 2009; Tuller et al. 2010; Prabhakaran et al. 2015).”