English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Protein synthesis in E. coli : dependence of codon-specific elongation on tRNA concentration and codon usage

MPS-Authors
/persons/resource/persons121790

Rudorf,  Sophia
Reinhard Lipowsky, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

/persons/resource/persons121584

Lipowsky,  Reinhard
Reinhard Lipowsky, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

2180975.pdf
(Publisher version), 3MB

Supplementary Material (public)

2180975_supp.pdf
(Supplementary material), 172KB

Citation

Rudorf, S., & Lipowsky, R. (2015). Protein synthesis in E. coli: dependence of codon-specific elongation on tRNA concentration and codon usage. PLoS One, 10(8): e0134994. doi:10.1371/journal.pone.0134994.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-4B2C-1
Abstract
To synthesize a protein, a ribosome moves along a messenger RNA (mRNA), reads it codon by codon, and takes up the corresponding ternary complexes which consist of aminoacylated transfer RNAs (aa-tRNAs), elongation factor Tu (EF-Tu), and GTP. During this process of translation elongation, the ribosome proceeds with a codon-specific rate. Here, we present a general theoretical framework to calculate codon-specific elongation rates and error frequencies based on tRNA concentrations and codon usages. Our theory takes three important aspects of <italic>in-vivo</italic> translation elongation into account. First, non-cognate, near-cognate and cognate ternary complexes compete for the binding sites on the ribosomes. Second, the corresponding binding rates are determined by the concentrations of free ternary complexes, which must be distinguished from the total tRNA concentrations as measured <italic>in vivo</italic>. Third, for each tRNA species, the difference between total tRNA and ternary complex concentration depends on the codon usages of the corresponding cognate and near-cognate codons. Furthermore, we apply our theory to two alternative pathways for tRNA release from the ribosomal E site and show how the mechanism of tRNA release influences the concentrations of free ternary complexes and thus the codon-specific elongation rates. Using a recently introduced method to determine kinetic rates of <italic>in-vivo</italic> translation from <italic>in-vitro</italic> data, we compute elongation rates for all codons in <italic>Escherichia coli</italic>. We show that for some tRNA species only a few tRNA molecules are part of ternary complexes and, thus, available for the translating ribosomes. In addition, we find that codon-specific elongation rates strongly depend on the overall codon usage in the cell, which could be altered experimentally by overexpression of individual genes.