Rare Human Codons and HCMV Translational Regulation

2017 ◽  
Vol 27 (4) ◽  
pp. 213-216 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Protein Synthesis ◽  
Codon Usage ◽  
Human Cytomegalovirus ◽  
Translational Regulation ◽  
Protein Production ◽  
Nucleotide Sequences ◽  
Positive Correlation ◽  
Human Host ◽  
Rare Codons

Restriction of protein synthesis characterizes human cytomegalovirus (HCMV) latency in the human host. In analyzing the molecular factors that hinder HCMV expression, the present study shows that HCMV genes frequently use 6 rare codons, i.e., GCG (Ala), CCG (Pro), CGT (Arg), CGC (Arg), TCG (Ser), and ACG (Thr). In some instances, the rare host codons are clustered along viral nucleotide sequences and represent the majority in sequences encoding short alanine and proline repeats. Given the positive correlation between codon usage, tRNA content, and protein production, the results support the hypothesis that HCMV usage of rare human codons might hinder HCMV protein synthesis, in this way leading to HCMV latency.

Adaptation to stress in yeast: to translate or not?

2012 ◽  
Vol 40 (4) ◽  
pp. 794-799 ◽  
Author(s):  
Clare E. Simpson ◽  
Mark P. Ashe
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Stress Responses ◽  
Translational Regulation ◽  
Protein Production ◽  
Yeast Cells ◽  
Specific Proteins ◽  
Response To Stress ◽  
Eukaryotic Organisms ◽  
The Impact

For most eukaryotic organisms, including Saccharomyces cerevisiae, the rapid inhibition of protein synthesis forms part of a response to stress. In order to balance the changing conditions, precise stress-specific alterations to the cell's proteome are required. Therefore, in the background of a global down-regulation in protein synthesis, specific proteins are induced. Given the level of plasticity required to enable stress-specific alterations of this kind, it is surprising that the mechanisms of translational regulation are not more diverse. In the present review, we summarize the impact of stress on translation initiation, highlighting both the similarities and distinctions between various stress responses. Finally, we speculate as to how yeast cells generate stress-responsive programmes of protein production when regulation is focused on the same steps in the translation pathway.

scholarly journals Development and comparison of cell-free protein synthesis systems derived from typical bacterial chassis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Liyuan Zhang ◽  
Xiaomei Lin ◽  
Ting Wang ◽  
Wei Guo ◽  
Yuan Lu
Keyword(s):  
Protein Synthesis ◽  
Protein Production ◽  
Influential Factors ◽  
Competent Cell ◽  
Free Protein ◽  
Application Range ◽  
E Coli ◽  
Short Time ◽  
Cell Free Protein Synthesis

AbstractCell-free protein synthesis (CFPS) systems have become an ideal choice for pathway prototyping, protein production, and biosensing, due to their high controllability, tolerance, stability, and ability to produce proteins in a short time. At present, the widely used CFPS systems are mainly based on Escherichia coli strain. Bacillus subtilis, Corynebacterium glutamate, and Vibrio natriegens are potential chassis cells for many biotechnological applications with their respective characteristics. Therefore, to expand the platform of the CFPS systems and options for protein production, four prokaryotes, E. coli, B. subtilis, C. glutamate, and V. natriegens were selected as host organisms to construct the CFPS systems and be compared. Moreover, the process parameters of the CFPS system were optimized, including the codon usage, plasmid synthesis competent cell selection, plasmid concentration, ribosomal binding site (RBS), and CFPS system reagent components. By optimizing and comparing the main influencing factors of different CFPS systems, the systems can be optimized directly for the most influential factors to further improve the protein yield of the systems. In addition, to demonstrate the applicability of the CFPS systems, it was proved that the four CFPS systems all had the potential to produce therapeutic proteins, and they could produce the receptor-binding domain (RBD) protein of SARS-CoV-2 with functional activity. They not only could expand the potential options for in vitro protein production, but also could increase the application range of the system by expanding the cell-free protein synthesis platform.

Nucleotide sequences required for the regulation of a rat alpha 2u-globulin gene by glucocorticoids

1986 ◽  
Vol 6 (7) ◽  
pp. 2334-2346
Author(s):  
W R Addison ◽  
D T Kurtz
Keyword(s):  
Protein Synthesis ◽  
Unknown Function ◽  
Opposite Effect ◽  
Nucleotide Sequences ◽  
Secondary Response ◽  
L Cells ◽  
Mutant Genes ◽  
Globulin Gene

alpha 2u-Globulin is a rat protein of as yet unknown function whose synthesis can be induced by glucocorticoids and several other hormones. Induction by glucocorticoids is a secondary response to the hormone: protein synthesis is required before the hormone can exert its stimulatory effect on alpha 2u-globulin transcription. We have used the linker-scanning mutagenesis procedure, followed by transfer of the mutant genes into mouse L-cells for analysis of their phenotype, to determine sequences within a cloned alpha 2u-globulin promoter that are required for its regulation by glucocorticoids. Mutations between positions -115 and -160 abolish or greatly reduce the inducibility of alpha 2u-globulin by the hormone. Mutations just upstream from this region, between positions -177 and -220, have an opposite effect; they increase induction two- to fourfold.

Translational regulation of ribosomal protein synthesis during xenopus development

1989 ◽  
Vol 27 ◽  
pp. 219
Author(s):  
B. Cardinali ◽  
C. Bagni ◽  
F. Amaldi ◽  
N. Campioni ◽  
P. Mariottini ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Translational Regulation ◽  
Xenopus Development ◽  
Ribosomal Protein Synthesis

scholarly journals Role of CDK1 in Translational Regulation in the M-Phase

2020 ◽  
Author(s):  
Jaroslav Kalous ◽  
Denisa Jansova ◽  
Andrej Susor
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Translational Regulation ◽  
Gene Expression Regulation ◽  
Translational Initiation ◽  
Initiation Factors ◽  
Cellular Events ◽  
M Phase ◽  
Mitosis And Meiosis

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

scholarly journals Synonymous lysine codon usage modification in a mobile antibiotic resistance gene similarly alters protein production in bacterial species with divergent lysine codon usage biases because it removes a duplicate AAA lysine codon

2018 ◽  
Author(s):  
Mohammed Alorabi ◽  
Aisha M. AlAmri ◽  
Yuiko Takebayashi ◽  
Kate J. Heesom ◽  
Matthew B. Avison
Keyword(s):  
Antibiotic Resistance ◽  
Codon Usage ◽  
Resistance Gene ◽  
Codon Bias ◽  
Protein Production ◽  
Bacterial Species ◽  
Antibiotic Resistance Gene ◽  
Site Directed Mutagenesis ◽  
Acinetobacter Baumanii ◽  
Highly Expressed Genes

AbstractThe mobile antibiotic resistance gene blaIMP-1 is clinically important and has a synonymous AAA:AAG lysine codon usage bias of 73:27. This bias is like that seen in experimentally determined highly expressed genes in Escherichia coli and Acinetobacter baumanii, but quite different from that seen in Pseudomonas aeruginosa (26:74 AAA:AAG). Here we show that, paradoxically, shifting the AAA:AAG lysine codon bias to 8:92 in blaIMP-1 expressed from a natural promoter results in significantly more IMP-1 production in all three species. Sequential site directed mutagenesis revealed that increased IMP-1 production occurs following removal of an AAA,AAA double lysine codon and that otherwise, lysine codon usage had no observable impact on IMP-1 production. We conclude that ribosomal slippage at this poly-adenosine region reduces efficient translation of IMP-1 and that punctuating the region with guanine reduces ribosomal slippage and increases IMP-1 production.

Translational Regulation of Eukaryotic Protein Synthesis by Phosphorylation of eIF-2α

1985 ◽  
pp. 515-543 ◽  
Author(s):  
IRVING M. LONDON ◽  
DANIEL H. LEVIN ◽  
ROBERT L. MATTS ◽  
N. SHAUN B. THOMAS ◽  
RAYMOND PETRYSHYN ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translational Regulation ◽  
Eukaryotic Protein

scholarly journals The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid

2019 ◽  
Vol 11 (9) ◽  
pp. 2439-2456 ◽  
Author(s):  
Lucía D’Andrea ◽  
Francisco-Javier Pérez-Rodríguez ◽  
Montserrat de Castellarnau ◽  
Susana Guix ◽  
Enric Ribes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Sequence Space ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Critical Role ◽  
Translation Efficiency ◽  
Rare Codons ◽  
Codon Composition ◽  
Cellular Genome

AbstractHepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype–phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype–phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff—not naturally occurring in HAV infection—involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.

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