Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate

Thomas E. Gorochowski, Zoya Ignatova, Roel A L Bovenberg, J. Roubos

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Translation of protein from mRNA is a complex multistep process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.

Original languageEnglish
Pages (from-to)3022-3032
Number of pages11
JournalNucleic Acids Research
Volume43
Issue number6
DOIs
Publication statusPublished - 2015

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Transfer RNA
Codon
Ribosomes
Messenger RNA
Protein Biosynthesis
Proteins
Proteome
Saccharomyces cerevisiae
Theoretical Models
Genome
Escherichia coli
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate. / Gorochowski, Thomas E.; Ignatova, Zoya; Bovenberg, Roel A L; Roubos, J.

In: Nucleic Acids Research, Vol. 43, No. 6, 2015, p. 3022-3032.

Research output: Contribution to journalArticle

Gorochowski, Thomas E. ; Ignatova, Zoya ; Bovenberg, Roel A L ; Roubos, J. / Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate. In: Nucleic Acids Research. 2015 ; Vol. 43, No. 6. pp. 3022-3032.
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