Efficient Manipulations of Synonymous Mutations for Controlling Translation Rate: An Analytical Approach

2012 ◽  
Vol 19 (2) ◽  
pp. 200-231 ◽  
Author(s):  
Alexandra Dana ◽  
Tamir Tuller
Keyword(s):  
Analytical Approach ◽  
Translation Rate ◽  
Synonymous Mutations

scholarly journals Differential proteostatic regulation of insoluble and abundant proteins

2019 ◽  
Vol 35 (20) ◽  
pp. 4098-4107 ◽  
Author(s):  
Reshmi Ramakrishnan ◽  
Bert Houben ◽  
Frederic Rousseau ◽  
Joost Schymkowitz
Keyword(s):  
Fluorescent Protein ◽  
Meta Analysis ◽  
Trigger Factor ◽  
Supplementary Information ◽  
Translational Efficiency ◽  
Translation Rate ◽  
Synonymous Mutations ◽  
Metabolic Functions ◽  
Client Proteins ◽  
Green Fluorescent

Abstract Motivation Despite intense effort, it has been difficult to explain chaperone dependencies of proteins from sequence or structural properties. Results We constructed a database collecting all publicly available data of experimental chaperone interaction and dependency data for the Escherichia coli proteome, and enriched it with an extensive set of protein-specific as well as cell-context-dependent proteostatic parameters. Employing this new resource, we performed a comprehensive meta-analysis of the key determinants of chaperone interaction. Our study confirms that GroEL client proteins are biased toward insoluble proteins of low abundance, but for client proteins of the Trigger Factor/DnaK axis, we instead find that cellular parameters such as high protein abundance, translational efficiency and mRNA turnover are key determinants. We experimentally confirmed the finding that chaperone dependence is a function of translation rate and not protein-intrinsic parameters by tuning chaperone dependence of Green Fluorescent Protein (GFP) in E.coli by synonymous mutations only. The juxtaposition of both protein-intrinsic and cell-contextual chaperone triage mechanisms explains how the E.coli proteome achieves combining reliable production of abundant and conserved proteins, while also enabling the evolution of diverging metabolic functions. Availability and implementation The database will be made available via http://phdb.switchlab.org. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Hsp90 dictates viral sequence space by balancing the evolutionary tradeoffs between protein stability, aggregation and translation rate

2017 ◽  
Author(s):  
Ron Geller ◽  
Sebastian Pechmann ◽  
Ashley Acevedo ◽  
Raul Andino ◽  
Judith Frydman
Keyword(s):  
Protein Stability ◽  
Stability Limit ◽  
Translation Rate ◽  
Aggregation Propensity ◽  
Synonymous Mutations ◽  
Protein Biogenesis ◽  
Domain Boundaries ◽  
Polypeptide Folding ◽  
Hsp90 Activity ◽  
Population Sequence

AbstractAcquisition of mutations is central to evolution but the detrimental effects of most mutations on protein folding and stability limit protein evolvability. Molecular chaperones, which suppress aggregation and facilitate polypeptide folding, are proposed to promote sequence diversification by buffering destabilizing mutations. However, whether and how chaperones directly control protein evolution remains poorly understood. Here, we examine the effect of reducing the activity of the key eukaryotic chaperone Hsp90 on poliovirus evolution. Contrary to predictions of a buffering model, inhibiting Hsp90 increases population sequence diversity and promotes accumulation of mutations reducing protein stability. Explaining this counterintuitive observation, we find that Hsp90 offsets the evolutionary tradeoff between protein stability and aggregation. Lower chaperone levels favor sequence variants of reduced hydrophobicity, thus decreasing protein aggregation propensity but at a cost to protein stability. Notably, reducing Hsp90 activity also promotes clusters of codon-deoptimized synonymous mutations at inter-domain boundaries, likely to promote local ribosomal slowdown to facilitate cotranslational domain folding. Our results reveal how a chaperone can shape the sequence landscape at both the protein and RNA levels to harmonize the competing constraints posed by protein stability, aggregation propensity and translation rate on successful protein biogenesis.

scholarly journals Prediction of the Effects of Synonymous Variants on SARS-CoV-2 Genome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1053
Author(s):  
Wan Xin Boon ◽  
Boon Zhan Sia ◽  
Chong Han Ng
Keyword(s):  
Codon Usage ◽  
Rna Structure ◽  
Rna Virus ◽  
Synonymous Codon ◽  
Synonymous Codon Usage ◽  
Viral Fitness ◽  
Translation Rate ◽  
Synonymous Mutations ◽  
Global Initiative ◽  
The Stability

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple studies had been done to identify and study nonsynonymous mutations, which change amino acid residues of SARS-CoV-2 proteins. On the other hand, there is little study on the effects of SARS-CoV-2 synonymous mutations. Although these mutations do not alter amino acids, some studies suggest that they may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome.   Methods: A total of 30,229 SARS-CoV-2 genomic sequences were retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database and aligned using MAFFT. Then, the mutations and their respective frequency were identified. A prediction of RNA secondary structures and their base pair probabilities was performed to study the effect of synonymous mutations on RNA structure and stability. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2.  Results: A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a, followed by C313U and C9286U mutation in nsp1 and nsp4 of ORF1a, respectively.   Conclusion: Among the synonymous mutations identified, C913U mutation in ORF1a and C26735U in membrane (M) protein may affect RNA secondary structure, reducing the stability of RNA folding and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

The Dynamics of TAT Process

2014 ◽  
Vol 35 (2) ◽  
pp. 103-133 ◽  
Author(s):  
Benoît Verdon ◽  
Catherine Chabert ◽  
Catherine Azoulay ◽  
Michèle Emmanuelli ◽  
Françoise Neau ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Analytical Approach ◽  
Therapeutic Process ◽  
Practice Research ◽  
Rorschach Test ◽  
Mental Functioning ◽  
Projective Tests ◽  
The Subject ◽  
Latent Content ◽  
Rigorous Method

After many years of clinical practice, research and the teaching of projective tests, Shentoub and her colleagues (Debray, Brelet, Chabert & al.) put forward an original and rigorous method of analysis and interpretation of the TAT protocols in terms of psychoanalysis and clinical psychopathology. They developed the TAT process theory in order to understand how the subject builds a narrative. Our article will emphasize the source of the analytical approach developed by V. Shentoub in the 1950s to current research; the necessity of marking the boundary between the manifest and latent content in the cards; the procedure for analyzing the narrative, supported by an analysis sheet for understanding the stories' structure and identifying the defense mechanisms; and how developing hypotheses about how the mental functions are organized, as well as their potential psychopathological characteristics; and the formulation of a diagnosis in psychodynamic terms. In conjunction with the analysis and interpretation of the Rorschach test, this approach allows us to develop an overview of the subject's mental functioning, taking into account both the psychopathological elements that may threaten the subject and the potential for a therapeutic process. We will illustrate this by comparing neurotic, borderline, and psychotic personalities.

Maxim Berezovsky C-dur symphony in a context of new biographical scenario of artist’s life-creativity

2018 ◽  
pp. 13-25
Author(s):  
Olha Shumilina
Keyword(s):  
Eighteenth Century ◽  
Instrumental Music ◽  
Analytical Approach ◽  
Spiritual Direction ◽  
Theoretical Research ◽  
Orchestral Music ◽  
Musical Life ◽  
Analysis And Synthesis ◽  
Mental Modeling ◽  
Independent Work

Relevance of the study. The article studies recently found symphony of the prominent Ukrainian composer of the second half of the eighteenth century Maxim Berezovsky. He is widely known now as the author of cyclic spiritual concerts written for the Orthodox worship, and is practically unknown as a musician instrumentalist associated with the imperial theater and the court musical life. The work of M. Berezovsky as a secular musician determined the creative interest in composing instrumental music intended for secular chamber and orchestral music. Main objective of the article is a clarification of M.Berezovsky symphony as one of secular field artworks in the light of new summaries about artist’s life-creativity. Methodology. Taking into account peculiarities of the material and the analytical approach to its study, the methods of theoretical research have been chosen(abstraction, analysis and synthesis, induction and deduction, mental modeling, ascension from abstract to concrete, etc.). Conclusions. As a result of a study the symphony analysis in a context of new authentic statements about M.Berezovsky’s life-creativity. It was stated that this artwork was written not accidentally and detects absolute awareness of the artist in all composer’s niceties – how to build a topic and build a homophonic construction based on it, in a technique of orchestral construction, form creations of that time and etc. From the beginning of his creative career, M. Berezovsky was well aware of the possibilities of the orchestra as a performer, attached to the Italian opera and instrumental music. Symphony enriches our imagination about the works of M. Berezovsky in the field of secular instrumental and operatic music and extends the range of works of the artist beyond the spiritual direction. Some signs indicate that the Symphony was not an independent work, but an overture to the opera Demofont.

Maxim Berezovsky C-dur symphony in a context of new biographical scenario of artist’s life-creativity

2018 ◽  
pp. 13-25
Author(s):  
Olha Shumilina
Keyword(s):  
Eighteenth Century ◽  
Instrumental Music ◽  
Analytical Approach ◽  
Spiritual Direction ◽  
Theoretical Research ◽  
Orchestral Music ◽  
Musical Life ◽  
Analysis And Synthesis ◽  
Mental Modeling ◽  
Independent Work

Relevance of the study. The article studies recently found symphony of the prominent Ukrainian composer of the second half of the eighteenth century Maxim Berezovsky. He is widely known now as the author of cyclic spiritual concerts written for the Orthodox worship, and is practically unknown as a musician instrumentalist associated with the imperial theater and the court musical life. The work of M. Berezovsky as a secular musician determined the creative interest in composing instrumental music intended for secular chamber and orchestral music. Main objective of the article is a clarification of M.Berezovsky symphony as one of secular field artworks in the light of new summaries about artist’s life-creativity. Methodology. Taking into account peculiarities of the material and the analytical approach to its study, the methods of theoretical research have been chosen(abstraction, analysis and synthesis, induction and deduction, mental modeling, ascension from abstract to concrete, etc.). Conclusions. As a result of a study the symphony analysis in a context of new authentic statements about M.Berezovsky’s life-creativity. It was stated that this artwork was written not accidentally and detects absolute awareness of the artist in all composer’s niceties – how to build a topic and build a homophonic construction based on it, in a technique of orchestral construction, form creations of that time and etc. From the beginning of his creative career, M. Berezovsky was well aware of the possibilities of the orchestra as a performer, attached to the Italian opera and instrumental music. Symphony enriches our imagination about the works of M. Berezovsky in the field of secular instrumental and operatic music and extends the range of works of the artist beyond the spiritual direction. Some signs indicate that the Symphony was not an independent work, but an overture to the opera Demofont.

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