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Landscapes of Ribosome Dwell Times and Relationships with Aminoacyl-tRNA Levels in Mammals

52 Pages Posted: 21 Aug 2019 Sneak Peek Status: Review Complete

See all articles by Cédric Gobet

Cédric Gobet

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering; Nestlé Research

Benjamin Dieter Weger

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering; Nestlé Research

Julien Marquis

Nestlé Research; University of Lausanne - Lausanne Genomic Technologies Facility

Eva Martin

Nestlé Research

Frédéric Gachon

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering; Nestlé Research; University of Queensland - Institute for Molecular Bioscience

Felix Naef

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering

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Abstract

Protein translation depends on mRNA-specific initiation, elongation and termination rates. While ribosome elongation is well studied in bacteria and yeast, less is known in higher eukaryotes. Here, we combined ribosome and tRNA profiling to investigate the relations between ribosome elongation rates, (aminoacyl-) tRNA levels, and codon usage in mammals. We modeled codon-specific ribosome dwell times and translation efficiencies from ribosome profiling, considering codon-pair interactions between ribosome sites. In mouse liver, the model revealed site- and codon-specific dwell times, as well as pairs of adjacent codons in the P and A site that markedly slow down or speed up elongation. While translation efficiencies varied significantly across diurnal time and feeding regimen, codon dwell times were highly stable and conserved in human. Measured tRNA levels correlated with codon usage and several tRNAs were lowly aminoacylated, which was conserved in fasted mice. Finally, we uncovered that the longest codon dwell times could be explained by lowly aminoacylated tRNAs, or high codon usage relative to tRNA abundance.

Keywords: ribosome profiling, Translation, mathematical modelling, tRNA, translation elongation, Bioinformatics, protein synthesis, Ribosome, Codons, aminoacylation, Mouse liver, systems biology

Suggested Citation

Gobet, Cédric and Weger, Benjamin Dieter and Marquis, Julien and Martin, Eva and Gachon, Frédéric and Naef, Felix, Landscapes of Ribosome Dwell Times and Relationships with Aminoacyl-tRNA Levels in Mammals (August 21, 2019). CELL-REPORTS-D-19-03229. Available at SSRN: https://ssrn.com/abstract=3439683 or http://dx.doi.org/10.2139/ssrn.3439683
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Cédric Gobet

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering ( email )

Lausanne, CH-1015
Switzerland

Nestlé Research ( email )

Lausanne, CH-1015
Switzerland

Benjamin Dieter Weger

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering ( email )

Lausanne, CH-1015
Switzerland

Nestlé Research ( email )

Lausanne, CH-1015
Switzerland

Julien Marquis

Nestlé Research ( email )

Lausanne, CH-1015
Switzerland

University of Lausanne - Lausanne Genomic Technologies Facility ( email )

Lausanne, CH-1015
Switzerland

Eva Martin

Nestlé Research ( email )

Lausanne, CH-1015
Switzerland

Frédéric Gachon

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering ( email )

Lausanne, CH-1015
Switzerland

Nestlé Research ( email )

Lausanne, CH-1015
Switzerland

University of Queensland - Institute for Molecular Bioscience ( email )

306 Carmody Road
Queensland Bioscience Precinct (Building 80)
St Lucia, Queensland 4072
Australia

Felix Naef (Contact Author)

Ecole Polytechnique Fédérale de Lausanne - Institute of Bioengineering ( email )

Lausanne, CH-1015
Switzerland

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