Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes

Ikemura, Toshimichi

doi:10.1016/0022-2836(81)90363-6

Cited by 800 publications

(405 citation statements)

References 60 publications

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“…mRNA folding | protein abundance | synonymous mutations | ribosome density | translation initiation S ynonymous mutations (mutations that alter the coding DNA and RNA sequence without affecting the amino acid sequence of the protein produced) can significantly influence protein abundance via changes in translation efficiency (1)(2)(3)(4)(5)(6)(7). Previous studies have suggested two main mechanisms by which protein abundance may be modulated by synonymous mutations: codon bias, denoting the differential usage of synonymous codons depending on the levels of their corresponding tRNAs in the cell (8), and the folding energy of the mRNA transcript, which may influence ribosome binding, and therefore translation initiation (5,9).…”

mentioning

confidence: 99%

Translation efficiency is determined by both codon bias and folding energy

Tuller

Waldman²,

Kupiec³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

502

598

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Synonymous mutations do not alter the protein produced yet can have a significant effect on protein levels. The mechanisms by which this effect is achieved are controversial; although some previous studies have suggested that codon bias is the most important determinant of translation efficiency, a recent study suggested that mRNA folding at the beginning of genes is the dominant factor via its effect on translation initiation. Using the Escherichia coli and Saccharomyces cerevisiae transcriptomes, we conducted a genome-scale study aiming at dissecting the determinants of translation efficiency. There is a significant association between codon bias and translation efficiency across all endogenous genes in E. coli and S. cerevisiae but no association between folding energy and translation efficiency, demonstrating the role of codon bias as an important determinant of translation efficiency. However, folding energy does modulate the strength of association between codon bias and translation efficiency, which is maximized at very weak mRNA folding (i.e., high folding energy) levels. We find a strong correlation between the genomic profiles of ribosomal density and genomic profiles of folding energy across mRNA, suggesting that lower folding energies slow down the ribosomes and decrease translation efficiency. Accordingly, we find that selection forces act near uniformly to decrease the folding energy at the beginning of genes. In summary, these findings testify that in endogenous genes, folding energy affects translation efficiency in a global manner that is not related to the expression levels of individual genes, and thus cannot be detected by correlation with their expression levels.mRNA folding | protein abundance | synonymous mutations | ribosome density | translation initiation

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mentioning

confidence: 99%

Translation efficiency is determined by both codon bias and folding energy

Tuller

Waldman²,

Kupiec³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

502

598

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“…This has already been well established, by other means, for translation; for instance, nonuniform usage of synonymous codons has been related to tRNA's abundance (Ikemura, 1981;Bulmer, 1987) and gene expressivity (Gouy and Gautier, 1982;Holm, 1986), has been explained in terms of ef ciency requirements by Grosjean and Fiers (1982).…”

Section: Resultsmentioning

confidence: 82%

Translation Conditional Models for Protein Coding Sequences

Rodolphe¹,

Mathé

2000

Journal of Computational Biology

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A coding sequence is de ned as a DNA sequence coding the primary structure of a protein (a polypeptide). Such a sequence must satisfy a speci c constraint, which consists in coding a functional protein. As the genetic code is degenerated, there exists, for a given polypeptide, a set of synonymous sequences which would code the same polypeptide. Translation conditional models are being de ned on such sets. The aim of this paper is to give a common formalism. Besides the codon bias model, a few other conditional models will be de ned. Statistical estimators and comparison methods will be brie y presented. These models can be used for gene classi cation, or to nd out, in a real sequence, remarkable features. An example will be presented on Escherichia coli genes.

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“…The significance of rare codons in regulatory and minor proteins has been studied before [15-201, and recently [21] it has been shown that the insertion in tandem of four of the extremely rare codon (Arg AGG) into the E. coli cut gene significantly reduces the level of expression. For some E. coli proteins the synonymous codons are used in a non-random manner and the codons preferred are those recognised by the most abundant tRNA species in the cell; the concentration of each tRNA and the frequency of usage of the synonymous codons have been listed by Ikamura [22,231. Codons AGA, AGG and CGG for arginine, CCC for proline, GGA for glycine, CUA for leucine were considered to be rare codons (Table2) and are also not present in the mRNA of major outer membrane proteins: lipoprotein [24], OmpA [25], OmpF [26], OmpC [27], and LamB [28].…”

Section: Discussionmentioning

confidence: 99%

Intermediates in the synthesis of TolC protein include an incomplete peptide stalled at a rare Arg codon

Misra

Reeves

1985

Eur J Biochem

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TolC is a minor outer membrane protein of Escherichia coli K 12 and is initially synthesized as a precursor. A distinct intermediate polypeptide of Mr about 46000 was consistently observed at the initial stages of biosynthesis. The further elongation of this peptide can be blocked by chloramphenicol. We have investigated the cause of the temporary accumulation of the 46000‐Mr intermediate and we postulate that the presence of a rare codon AGA (Arg) at codon 402 of the tolC mRNA halts translating ribosomes owing to a limiting amount of the tRNAArg (AGA) species in the cell. The translation of tolC mRNA can be increased by providing T4 tRNAArg(AGA), encoded on a plasmid.

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Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes

Cited by 800 publications

References 60 publications

Translation efficiency is determined by both codon bias and folding energy

Translation efficiency is determined by both codon bias and folding energy

Translation Conditional Models for Protein Coding Sequences

Intermediates in the synthesis of TolC protein include an incomplete peptide stalled at a rare Arg codon

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