ArticleMolecular systems biology2012
Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 132 citations in OpenAlex.
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- OPT: Codon optimize gene sequences for E. coli protein overexpression.Journal of molecular biology · 2025Article
- Viral codon usage and the virus-host interactions.Frontiers in microbiology · 2025Review
- Molecular insights into the inhibition of proton-activated chloride channel by transfer RNA.Cell research · 2024Article
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- Regulation of cGAS activity by RNA-modulated phase separation.EMBO reports · 2023Article
- On the gain of entrainment in theJournal of the Royal Society, Interface · 2023Article
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- Codon Usage and Context Analysis of Genes Modulated during SARS-CoV-2 Infection and Dental Inflammation.Vaccines · 2022Article
- Composition and Codon Usage Pattern Results in Divergence of theJournal of fungi (Basel, Switzerland) · 2022Article
- Increasing cell size remodels the proteome and promotes senescence.Molecular cell · 2022Article
- Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay.Nature communications · 2022Article
- The Ramp Atlas: facilitating tissue and cell-specific ramp sequence analyses through an intuitive web interface.NAR genomics and bioinformatics · 2022Article
- Cell Cycle-Dependent Transcription: The Cyclin Dependent Kinase Cdk1 Is a Direct Regulator of Basal Transcription Machineries.International journal of molecular sciences · 2022Review
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- Codon Usage Bias: An Endless Tale.Journal of molecular evolution · 2021Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
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.
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