Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels.

Authors

Milana Frenkel-Morgenstern, Department of Molecular Cell Biology, Weizmann Institute of Science; Department of Structural Biology, Weizmann Institute of Science; Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain
Tamar Danon, Department of Molecular Cell Biology, Weizmann Institute of Science
Thomas Christian, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Takao Igarashi, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Lydia Cohen, Department of Molecular Cell Biology, Weizmann Institute of Science
Ya-Ming Hou, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Lars Juhl Jensen, Disease Systems Biology, Novo Nordisk Foundation for Protein Research, Faculty of Health Sciences, University of Copenhagen

Document Type

Article

Publication Date

1-1-2012

Comments

This article has been peer reviewed. It was published in: Molecular Systems Biology.

Volume 8, 2012, Article number 572.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293633/. DOI: 10.1038/msb.2012.3.

Copyright © 2012 EMBO and Macmillan Publishers Limited. All rights reserved.

Abstract

The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins.

Recommended Citation

Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas; Igarashi, Takao; Cohen, Lydia; Hou, Ya-Ming; and Jensen, Lars Juhl, "Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels." (2012). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 62.
https://jdc.jefferson.edu/bmpfp/62

PubMed ID

22373820