Protein Expression from Measles (MV) L Protein Genes Optimized and Suboptimized to Human and Canine Codon Usage Bias Varies with Construct and Cell Type

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Akash Shah ◽  
Elizabeth W. Uhl ◽  
Michelle L. Osborn ◽  
Frank Michel ◽  
Robert J. Hogan
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Cell Type ◽  
L Protein

scholarly journals Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zhipeng Zhou ◽  
Yunkun Dang ◽  
Mian Zhou ◽  
Haiyan Yuan ◽  
Yi Liu
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Transcription Termination ◽  
Model Organism ◽  
Open Reading Frames ◽  
Strong Negative Correlation ◽  
Rare Codons ◽  
Cleavage And Polyadenylation ◽  
Mouse Cells

Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here, we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora, and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse cells. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression.

scholarly journals A New Look at Codon Usage and Protein Expression

10.29007/d4tz ◽  
2019 ◽  
Author(s):  
Gabriel Wright ◽  
Anabel Rodriguez ◽  
Patricia Clark ◽  
Scott Emrich
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Empirical Data ◽  
Codon Usage Bias ◽  
Elongation Rate ◽  
Translation Rate ◽  
Translation Elongation ◽  
Promising Alternative ◽  
Highly Expressed Genes ◽  
Adaptation Index

%MinMax, a model of intra-gene translational elongation rate, relies on codon usage frequencies. Historically, %MinMax has used tables that measure codon usage bias for all genes in an organism, such as those found at HIVE-CUT. In this paper, we provide evidence that codon usage bias based on all genes is insufficient to accurately measure absolute translation rate. We show that alternative ”High-φ” codon usage tables, generated by another model (ROC-SEMPPR), are a promising alternative. By creating a hybrid model, future codon usage analyses and their applications (e.g., codon harmonization) are likely to more accurately measure the ”tempo” of translation elongation. We also suggest a High- φ alternative to the Codon Adaptation Index (CAI), a classic metric of codon usage bias based on highly expressed genes. Significantly, our new alternative is equally well correlated with empirical data as traditional CAI without using experimentally determined expression counts as input.

scholarly journals Overcoming codon-usage bias in heterologous protein expression in Streptococcus gordonii

Microbiology ◽  
2009 ◽  
Vol 155 (11) ◽  
pp. 3581-3588 ◽  
Author(s):  
Song F. Lee ◽  
Yi-Jing Li ◽  
Scott A. Halperin
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Heterologous Protein ◽  
Trna Gene ◽  
Heterologous Protein Expression ◽  
Streptococcus Gordonii ◽  
Heterologous Proteins ◽  
Single Chain ◽  
Rare Codons

One of the limitations facing the development of Streptococcus gordonii into a successful vaccine vector is the inability of this bacterium to express high levels of heterologous proteins. In the present study, we have identified 12 codons deemed as rare codons in S. gordonii and seven other streptococcal species. tRNA genes encoding 10 of the 12 rare codons were cloned into a plasmid. The plasmid was transformed into strains of S. gordonii expressing the fusion protein SpaP/S1, the anti-complement receptor 1 (CR1) single-chain variable fragment (scFv) antibody, or the Toxoplasma gondii cyclophilin C18 protein. These three heterologous proteins contained high percentages of amino acids encoded by rare codons. The results showed that the production of SpaP/S1, anti-CR1 scFv and C18 increased by 2.7-, 120- and 10-fold, respectively, over the control strains. In contrast, the production of the streptococcal SpaP protein without the pertussis toxin S1 fragment was not affected by tRNA gene supplementation, indicating that the increased production of SpaP/S1 protein was due to the ability to overcome the limitation caused by rare codons required for the S1 fragment. The increase in anti-CR1 scFv production was also observed in Streptococcus mutans following tRNA gene supplementation. Collectively, the findings in the present study demonstrate for the first time, to the best of our knowledge, that codon-usage bias exists in Streptococcus spp. and the limitation of heterologous protein expression caused by codon-usage bias can be overcome by tRNA supplementation.

scholarly journals Distinct responses to rare codons in select Drosophila tissues

2022 ◽  
Author(s):  
Scott R. Allen ◽  
Rebeccah K Stewart ◽  
Michael Rogers ◽  
Ivan Jimenez Ruiz ◽  
Erez Cohen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Critical Role ◽  
Specific Protein ◽  
Human Testis ◽  
Rare Codon ◽  
Tissue Specific ◽  
Rare Codons ◽  
Drosophila Testis

Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index, to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in restricting protein expression of an evolutionarily young gene, RpL10Aa, to the Drosophila testis. Rare codon-mediated restriction of this testis-specific protein is critical for female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

scholarly journals Localized Optimization of Measles Virus (MV) Hemagglutinin (H) Gene to Human Codon Usage Bias Increases Protein Expression

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Elizabeth W. Uhl ◽  
Michelle L. Osborn ◽  
Frank Michel ◽  
Tomislav Jelesijevic ◽  
Robert J. Hogan
Keyword(s):  
Protein Expression ◽  
Codon Usage ◽  
Codon Usage Bias ◽  
Measles Virus ◽  
H Gene

scholarly journals Patterns of genome-wide codon usage bias in tobacco, tomato and potato

2021 ◽  
Vol 35 (1) ◽  
pp. 657-664
Author(s):  
Ali Mostafa Anwar ◽  
Maha Aljabri ◽  
Mohamed El-Soda
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Genome Wide
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