Correlation of codon bias measures with mRNA levels: analysis of transcriptome data from Escherichia coli

Goetz, Regina; Fuglsang, Anders

doi:10.1016/j.bbrc.2004.11.134

Cited by 77 publications

(56 citation statements)

References 14 publications

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“…The causes of the nonexpression include poor mRNA export to the cytoplasm (23) and inefficient translation because of differences in codon usage (24). Therefore, to improve HA expression in mammalian cells, the nucleotides of CHA5 were optimized with human codons (25), and the percentage of G/C was subsequently increased from 42% to 58% to provide better mRNA stability, processing, and nucleocytoplasmic transport (23). This HA gene was commercially synthesized and then inserted into the pVAX vector to create a consensus HA-based DNA vaccine (pCHA5).…”

Section: Resultsmentioning

confidence: 99%

A consensus–hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses

Chen

Cheng²,

Huang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

138

123

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H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these viruses to humans has been documented in over 380 cases, with a mortality rate of Ϸ60%. There is great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. An H5N1 influenza vaccine must, therefore, be an integral part of any pandemic preparedness plan. However, traditional methods of making influenza vaccines have yet to produce a candidate that could induce potently neutralizing antibodies against divergent strains of H5N1 influenza viruses. To address this need, we generated a consensus H5N1 hemagglutinin (HA) sequence based on data available in early 2006. This sequence was then optimized for protein expression before being inserted into a DNA plasmid (pCHA5). Immunizing mice with pCHA5, delivered intramuscularly via electroporation, elicited antibodies that neutralized a panel of virions that have been pseudotyped with the HA from various H5N1 viruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Moreover, immunization with pCHA5 in mice conferred complete (clades 1 and 2.2) or significant (clade 2.1) protection from H5N1 virus challenges. We conclude that this vaccine, based on a consensus HA, could induce broad protection against divergent H5N1 influenza viruses and thus warrants further study.

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Section: Resultsmentioning

confidence: 99%

A consensus–hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses

Chen

Cheng²,

Huang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

138

123

View full text Add to dashboard Cite

show abstract

“…However, we chose to use CAI rather than EST abundance in our reported analyses because not all genes in our data set were represented in either the C. incerta or the C. reinhardtii library and normalization steps were employed in the preparation of these libraries. In other systems, moreover, CAI has been shown to be as good as mRNA abundance in predicting protein abundance ( Jansen et al 2003) and the best codon-bias-derived surrogate for gene expression level (Goetz and Fuglsang 2005).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Rates and Expression Level in Chlamydomonas

et al. 2006

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In many biological systems, especially bacteria and unicellular eukaryotes, rates of synonymous and nonsynonymous nucleotide divergence are negatively correlated with the level of gene expression, a phenomenon that has been attributed to natural selection. Surprisingly, this relationship has not been examined in many important groups, including the unicellular model organism Chlamydomonas reinhardtii. Prior to this study, comparative data on protein-coding sequences from C. reinhardtii and its close noninterfertile relative C. incerta were very limited. We compiled and analyzed protein-coding sequences for 67 nuclear genes from these taxa; the sequences were mostly obtained from the C. reinhardtii EST database and our C. incerta EST data. Compositional and synonymous codon usage biases varied among genes within each species but were highly correlated between the orthologous genes of the two species. Relative rates of synonymous and nonsynonymous substitution across genes varied widely and showed a strong negative correlation with the level of gene expression estimated by the codon adaptation index. Our comparative analysis of substitution rates in introns of lowly and highly expressed genes suggests that natural selection has a larger contribution than mutation to the observed correlation between evolutionary rates and gene expression level in Chlamydomonas.

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“…Highly expressed genes are often enriched for optimal, high-frequency codons (Duret 2002;Goetz and Fuglsang 2005), and optimization of codon usage in a particular transcript can significantly alter the level of protein expression (Gustafsson et al 2004), suggesting that cellular concentrations of tRNAs may influence the rate of translation. Although a relationship between tRNA abundance and translational efficiency has been generally accepted (Novoa and Ribas de Pouplana 2012), recent ribosome profiling studies do not capture increased ribosomal pausing at rare codons (Ingolia et al 2011), leading to a renewed debate over this general assumption.…”

Section: Introductionmentioning

confidence: 99%

Integrated tRNA, transcript, and protein profiles in response to steroid hormone signaling

Bortle

Nichols

Ramos

et al. 2015

RNA

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The accurate and efficient transfer of genetic information into amino acid sequences is carried out through codon-anticodon interactions between mRNA and tRNA, respectively. In this way, tRNAs function at the interface between gene expression and protein synthesis. Whether tRNA levels are dynamically regulated and to what degree tRNA abundance influences the cellular proteome remains largely unexplored. Here we profile tRNA, transcript and protein levels in Drosophila Kc167 cells, a plasmatocyte cell line that, upon treatment with 20-hydroxyecdysone, differentiates into macrophages. We find that high abundance tRNAs associate with codons that are overrepresented in the Kc167 cell proteome, whereas tRNAs that are in low supply associate with codons that are underrepresented. Ecdysone-induced differentiation of Kc167 cells leads to changes in mRNA codon usage in a manner consistent with the developmental progression of the cell. At both early and late time points, ecdysone treatment concomitantly increases the abundance of tRNAThr(CGU), which decodes a differentiation-associated codon that becomes enriched in the macrophage proteome. These results together suggest that tRNA levels may provide a meaningful regulatory mechanism for defining the cellular proteomic landscape.

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Correlation of codon bias measures with mRNA levels: analysis of transcriptome data from Escherichia coli

Cited by 77 publications

References 14 publications

A consensus–hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses

A consensus–hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses

Evolutionary Rates and Expression Level in Chlamydomonas

Integrated tRNA, transcript, and protein profiles in response to steroid hormone signaling

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