Synonymous codon usage regulates translation initiation
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ABSTRACT:
PROVIDER: PRJNA837608 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ribo-seq with firefly luciferase optimality reporters to determine whether incomplete translation and/or inhibited translation initiation is responsible for the reduced ribosome occupancy on nonoptimal transcripts.
2022-05-16 | GSE202900 | GEO
Project description:In yeast and mammals, activated GCN2 can phosphorylate its substrate eIF2α, which is a part of the eIF2-GTP-Met-tRNAiMet ternary complex. The eIF2α phosphorylation blocks the ternary complex formation and therefore inhibits translation initiation. Meanwhile, GCN2 activation associates with ribosomes and some translation elongation factors such as eEF1A. In Neurospora crassa, the homolog of GCN2 is CPC-3. Ribosome profiling and accompanying RNA-seq experiments in this project were used to explore the effects of CPC-3 on translation kinetics. Here we show that poor codon usage of mRNAs with long CDS preferentially causes CPC-3 activation, which in turn suppresses the translation initiation and elongation in both codon usage and CDS length dependent manner.
2021-08-10 | GSE168595 | GEO
Project description:Codon usage and protein length-dependent feedback from translation elongation to translation initiation and kinetics
| PRJNA708348 | ENA
Project description:Usage of synonymous codons represents a characteristic pattern of preference in each organism. It has been inferred that such bias of codon usage has evolved as a result of adaptation for efficient synthesis of proteins. Here we examined synonymous codon usage in genes of the fission yeast Schizosaccharomyces pombe, and compared codon usage bias with expression levels of the gene. In this organism, synonymous codon usage bias was correlated with expression levels of the gene; the bias was most obvious in two-codon amino acids. A similar pattern of the codon usage bias was also observed in Saccharomyces cerevisiae, Arabidopsis thaliana, and Caenorhabditis elegans, but was not obvious in Oryza sativa, Drosophila melanogaster, Takifugu rubripes and Homo sapiens. As codons of the highly expressed genes have greater influence on translational efficiency than codons of genes expressed at lower levels, it is likely that codon usage in the S. pombe genome has been optimized by translational selection through evolution. Relative amounts of mRNA for each ORF were measured by DNA microarray using genomic DNA as a reference, and the copy number of mRNA was calculated using an estimate of the total mRNA number in the cell as 100,000 copies.
2010-06-20 | E-GEOD-13554 | biostudies-arrayexpress
Project description:Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy and protein folding based on the assumption that codon usage affects translation dynamics. The role of codon usage in regulating translation, however, is not clear and has been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the use of preferred codons enhances the rate of translation elongation, whereas non-optimal codons slow translation. In addition, codon usage regulates ribosome traffic on the mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with substrate mRNAs manipulated to increase signal over background noise. We further show that codon usage plays an important role in regulating protein function by affecting co-translational protein folding. Together, these results resolve a long-standing fundamental question and demonstrate the importance of codon usage on protein folding.
2015-07-18 | GSE71032 | GEO
Project description:Messenger RNA (mRNA) stability substantially impacts steady-state gene expression levels in a cell. mRNA stability is strongly affected by codon composition in a translation-dependent manner across species, through a mechanism termed codon optimality. We have developed iCodon (www.iCodon.org), an algorithm for customizing mRNA expression through the introduction of synonymous codon substitutions into the coding sequence. iCodon is optimized for four vertebrate transcriptomes: mouse, human, frog, and fish. Users can predict the mRNA stability of any coding sequence based on its codon composition and subsequently generate more stable (optimized) or unstable (deoptimized) variants encoding for the same protein. Further, we show that codon optimality predictions correlate with both mRNA stability using a massive reporter library and expression levels using fluorescent reporters and analysis of endogenous gene expression in zebrafish embryos and/or human cells. Therefore, iCodon will benefit basic biological research, as well as a wide range of applications for biotechnology and biomedicine.
2022-07-09 | GSE207584 | GEO
Project description:The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias on regulating cell state-specific expression programs is currently debated. Here, we asked whether the gene expression program in the well-defined cell states of self-renewal and differentiation in embryonic stem cells is driven by optimized codon usage. Using ribosome and transcriptome profiling, we identified distinct codon signatures for human self-renewing and differentiating embryonic stem cells. One driver for the cell state-specific codon bias was the genomic GC-content of the differentially expressed genes and thus, determined by transcription rather than translation. However, by measuring the codon frequencies at the ribosome’s active sites interacting with transfer RNAs (tRNA), we discovered that the wobble position tRNA modification inosine strongly influenced the codon optimization in self-renewing embryonic stem cells. This effect was conserved in mice and independent of the differentiation stimulus. In summary, we newly reveal how translational mechanisms based on RNA modifications can shape optimized codon usage in embryonic stem cells.
2019-05-17 | GSE112085 | GEO
Project description:The uneven use of synonymous codons in the transcriptome regulates the efficiency and fidelity of protein translation rates. Yet, the importance of this codon bias on regulating cell state-specific expression programs is currently debated. Here, we asked whether the gene expression program in the well-defined cell states of self-renewal and differentiation in embryonic stem cells is driven by optimized codon usage. Using ribosome and transcriptome profiling, we identified distinct codon signatures for human self-renewing and differentiating embryonic stem cells. One driver for the cell state-specific codon bias was the genomic GC-content of the differentially expressed genes and thus, determined by transcription rather than translation. However, by measuring the codon frequencies at the ribosome’s active sites interacting with transfer RNAs (tRNA), we discovered that the wobble position tRNA modification inosine strongly influenced the codon optimization in self-renewing embryonic stem cells. This effect was conserved in mice and independent of the differentiation stimulus. In summary, we newly reveal how translational mechanisms based on RNA modifications can shape optimized codon usage in embryonic stem cells.
2019-05-17 | GSE123608 | GEO
Project description:Usage of synonymous codons represents a characteristic pattern of preference in each organism. It has been inferred that such bias of codon usage has evolved as a result of adaptation for efficient synthesis of proteins. Here we examined synonymous codon usage in genes of the fission yeast Schizosaccharomyces pombe, and compared codon usage bias with expression levels of the gene. In this organism, synonymous codon usage bias was correlated with expression levels of the gene; the bias was most obvious in two-codon amino acids. A similar pattern of the codon usage bias was also observed in Saccharomyces cerevisiae, Arabidopsis thaliana, and Caenorhabditis elegans, but was not obvious in Oryza sativa, Drosophila melanogaster, Takifugu rubripes and Homo sapiens. As codons of the highly expressed genes have greater influence on translational efficiency than codons of genes expressed at lower levels, it is likely that codon usage in the S. pombe genome has been optimized by translational selection through evolution.
2009-04-01 | GSE13554 | GEO
Project description:Selection of the translation start codon is a key step during protein synthesis in human cells. We obtained cryo-EM structures of human 48S initiation complexes and characterized the intermediates of codon recognition by kinetic methods using eIF1A as a reporter. Both approaches capture two distinct ribosome populations formed on an mRNA with a cognate AUG codon in the presence of eIF1A, eIF1, eIF2–GTP–Met-tRNAiMet, eIF3, eIF4A and eIF4B. The ‘open’ 40S subunit conformation differs from the human 48S scanning complex and represents an intermediate preceding the codon recognition step. The ‘closed’ form is similar to reported structures of complexes from yeast and mammals formed upon codon recognition, except for the orientation of eIF1A, which is unique in our structure. Kinetic experiments show how various initiation factors mediate the population distribution of open and closed conformations until 60S subunit docking. Our results provide insights into the timing and structure of human translation initiation intermediates and suggest the differences in the mechanisms of start codon selection between mammals and yeast.
2022-06-09 | PXD031985 | Pride