scholarly journals Widespread positive selection for mRNA secondary structure at synonymous sites in domesticated yeast

2019 ◽  
Author(s):  
Minghao Yu ◽  
Wenna Guo ◽  
Qiang Wang ◽  
Jian-Qun Chen
Keyword(s):  
Secondary Structure ◽  
Positive Selection ◽  
Yeast Genome ◽  
Cellular Respiration ◽  
Translational Efficiency ◽  
Mrna Secondary Structure ◽  
Frequency Spectra ◽  
Mrna Structure ◽  
Synonymous Sites ◽  
Selection For

AbstractmRNA secondary structure assumes a critical role in gene regulation, especially for translational efficiency. Previous studies have a growing appreciation of purifying selection for the conserved mRNA structure across lineages of different species. However, the effect of mRNA structure on positive evolution remains unclear. Here, we construct a large-scale dataset of single nucleotide polymorphisms (SNPs) at synonymous sites in the population of Saccharomyces cerevisiae, combined with the experimental assessment of mRNA structure, and perform empirical population genetics data analysis through unfolded site-frequency spectra. Our results suggest that functional mRNA stem drives faster evolution of increasing GC contents itself with the purpose of regulating translational speed, which is greatly influenced by length. At the synonymous site without codon usage bias, this kind of positive selection still exists. Furthermore, mRNA secondary structure is subject to positive selection widespread among the yeast genome, particularly related to mitochondria activities, which is possibly aimed to achieve a balance between cellular respiration and alcoholic fermentation precisely at a non-protein level. It is conducive to the adaption of the dramatic environment alterations from wild to man-made environments during the domestication.

scholarly journals Hypertrophic cardiomyopathy MYH7 mutation R723G alters mRNA secondary structure

2020 ◽  
Vol 52 (1) ◽  
pp. 15-19
Author(s):  
J. Rose ◽  
T. Kraft ◽  
B. Brenner ◽  
J. Montag
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Secondary Structure ◽  
Experimental Evidence ◽  
Point Mutation ◽  
Shape Analysis ◽  
Allelic Imbalance ◽  
Mrna Secondary Structure ◽  
Wild Type ◽  
Mrna Structure

Point mutation R723G in the MYH7 gene causes hypertrophic cardiomyopathy (HCM). Heterozygous patients with this mutation exhibit a comparable allelic imbalance of the MYH7 gene. On average 67% of the total MYH7 mRNA are derived from the MYH7R723G-allele and 33% from the MYH7WT allele. Mechanisms underlying mRNA allelic imbalance are largely unknown. We suggest that a different mRNA lifetime of the alleles may cause the allelic drift in R723G patients. A potent regulator of mRNA lifetime is its secondary structure. To test for alterations in the MYH7R723G mRNA structure we used selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) analysis. We show significantly different SHAPE reactivity of wild-type and MYH7R723G RNA, which is in accordance with bioinformatically predicted structures. Thus, we provide the first experimental evidence for mRNA secondary structure alterations by the HCM point mutation. We assume that this may result in a prolonged lifetime of MYH7R723G mRNA in vivo and subsequently in the determined allelic imbalance.

The involvement of mRNA secondary structure in protein synthesis

1987 ◽  
Vol 65 (6) ◽  
pp. 576-581 ◽  
Author(s):  
Jerry Pelletier ◽  
Nahum Sonenberg
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Binding Proteins ◽  
Atp Hydrolysis ◽  
Mrna Translation ◽  
Noncoding Region ◽  
Translational Efficiency ◽  
Mrna Secondary Structure ◽  
Complex Process ◽  
Eukaryotic Mrnas

Translation initiation in eukaryotes is a complex process involving many factors. A key step in this process is the binding of mRNA to the 43S preinitiation complex. This is generally the rate-limiting step in translation initiation and consequently a major determinant of mRNA translational efficiency. The primary and secondary structure of the mRNA 5′ noncoding region have been implicated in modulating translational efficiency. Translational efficiency was shown to be inversely proportional to the degree of secondary structure at the mRNA 5′ noncoding region. Furthermore, it was shown that cap-binding proteins that interact with the 5′ cap structure (m7GpppN) of eukaryotic mRNAs are involved in the "unwinding" of the mRNA secondary structure, in an ATP hydrolysis mediated event, to facilitate ribosome binding. Thus, cap-binding proteins can potentially regulate mRNA translation. Here, we discuss the available data supporting the notion that eukaryotic 5′ mRNA secondary structure plays an important role in translation initiation and the possible regulation of this process.

Leader length and secondary structure modulate mRNA function under conditions of stress

1988 ◽  
Vol 8 (7) ◽  
pp. 2737-2744
Author(s):  
M Kozak
Keyword(s):  
Secondary Structure ◽  
Simian Virus 40 ◽  
Inhibitory Effect ◽  
Simian Virus ◽  
Leader Sequence ◽  
Structural Basis ◽  
Translational Efficiency ◽  
Hypertonic Stress ◽  
Mrna Structure ◽  
Cellular Mrnas

Simian virus 40-based plasmids that direct the synthesis of preproinsulin in cultured monkey cells were used to study the effects of mRNA structure on translational efficiency. Lengthening the leader sequence enhanced translation in this system. The enhancement was most obvious when an unstructured sequence (two, four, or eight copies of the oligonucleotide AGCTAAGTAAGTAAGTA) was inserted upstream from a region of deliberate secondary structure; the degree of enhancement was proportional to the number of copies of the inserted oligonucleotide. Lengthening the leader sequence on the 3' side of a stem-and-loop structure, in contrast, did not offset the potentially inhibitory effect of the hairpin structure. Both the facilitating effect of length and the inhibitory effect of secondary structure were demonstrated most easily under conditions of mRNA competition, which was brought about by an abrupt shift in the tonicity of the culture medium. These experiments suggest a simple structural basis for the long-recognized differential response of viral and cellular mRNAs to hypertonic stress. The fact that the translatability of structure-prone mRNAs varies with changes in the environment may also have general implications for gene expression in eucaryotic cells.

scholarly journals Signs of Selection in Synonymous Sites of the Mitochondrial Cytochrome b Gene of Baikal Oilfish (Comephoridae) by mRNA Secondary Structure Alterations

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Veronika I. Teterina ◽  
Anatoliy M. Mamontov ◽  
Lyubov V. Sukhanova ◽  
Sergei V. Kirilchik
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Cytochrome B ◽  
Cytochrome B Gene ◽  
Mitochondrial Cytochrome ◽  
Mrna Secondary Structure ◽  
Synonymous Mutations ◽  
Mitochondrial Cytochrome B ◽  
Mitochondrial Cytochrome B Gene ◽  
Synonymous Sites

Studies over the past decade have shown a significant role of synonymous mutations in posttranscriptional regulation of gene expression, which is particularly associated with messenger RNA (mRNA) secondary structure alterations. Most studies focused on prokaryote genomes and the nuclear genomes of eukaryotes while little is known about the regulation of mitochondrial DNA (mtDNA) gene expression. This paper reveals signs of selection in synonymous sites of the mitochondrial cytochrome b gene (Cytb) of Baikal oilfish or golomyankas (Comephoridae) directed towards altering the secondary structure of the mRNA and probably altering the character of mtDNA gene expression. Our findings are based on comparisons of intraspecific genetic variation patterns of small golomyanka (Comephorus dybowski) and two genetic groups of big golomyanka (Comephorus dybowskii). Two approaches were used: (i) analysis of the distribution of synonymous mutations between weak-AT (W) and strong-GC (S) nucleotides within species and groups in accordance with mutation directions from central to peripheral haplotypes and (ii) approaches based on the predicted mRNA secondary structure.

scholarly journals Avoidance of stochastic RNA interactions can be harnessed to control protein expression levels in bacteria and archaea

2015 ◽  
Author(s):  
Sinan Uğur Umu ◽  
Anthony M. Poole ◽  
Renwick C. J. Dobson ◽  
Paul P. Gardner
Keyword(s):  
Codon Usage ◽  
Gene Expression Analysis ◽  
Fluorescent Protein ◽  
Translational Efficiency ◽  
Protein Abundance ◽  
Global Factor ◽  
Mrna Structure ◽  
Selection For ◽  
Green Fluorescent ◽  
Control Protein

AbstractA critical assumption of gene expression analysis is that mRNA abundances broadly correlate with protein abundance, but these two are often imperfectly correlated. Some of the discrepancy can be accounted for by two important mRNA features: codon usage and mRNA secondary structure. We present a new global factor, called mRNA:ncRNA avoidance, and provide evidence that avoidance increases translational efficiency. We also demonstrate a strong selection for avoidance of stochastic mRNA:ncRNA interactions across prokaryotes, and that these have a greater impact on protein abundance than mRNA structure or codon usage. By generating synonymously variant green fluorescent protein (GFP) mRNAs with different potential for mRNA:ncRNA interactions, we demonstrate that GFP levels correlate well with interaction avoidance. Therefore, taking stochastic mRNA:ncRNA interactions into account enables precise modulation of protein abundance.

scholarly journals Avoidance of stochastic RNA interactions can be harnessed to control protein expression levels in bacteria and archaea

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sinan Uğur Umu ◽  
Anthony M Poole ◽  
Renwick CJ Dobson ◽  
Paul P Gardner
Keyword(s):  
Codon Usage ◽  
Gene Expression Analysis ◽  
Fluorescent Protein ◽  
Translational Efficiency ◽  
Protein Abundance ◽  
Global Factor ◽  
Mrna Structure ◽  
Selection For ◽  
Green Fluorescent ◽  
Control Protein

A critical assumption of gene expression analysis is that mRNA abundances broadly correlate with protein abundance, but these two are often imperfectly correlated. Some of the discrepancy can be accounted for by two important mRNA features: codon usage and mRNA secondary structure. We present a new global factor, called mRNA:ncRNA avoidance, and provide evidence that avoidance increases translational efficiency. We also demonstrate a strong selection for the avoidance of stochastic mRNA:ncRNA interactions across prokaryotes, and that these have a greater impact on protein abundance than mRNA structure or codon usage. By generating synonymously variant green fluorescent protein (GFP) mRNAs with different potential for mRNA:ncRNA interactions, we demonstrate that GFP levels correlate well with interaction avoidance. Therefore, taking stochastic mRNA:ncRNA interactions into account enables precise modulation of protein abundance.

scholarly journals Leader length and secondary structure modulate mRNA function under conditions of stress.

1988 ◽  
Vol 8 (7) ◽  
pp. 2737-2744 ◽  
Author(s):  
M Kozak
Keyword(s):  
Secondary Structure ◽  
Simian Virus 40 ◽  
Inhibitory Effect ◽  
Simian Virus ◽  
Leader Sequence ◽  
Structural Basis ◽  
Translational Efficiency ◽  
Hypertonic Stress ◽  
Mrna Structure ◽  
Cellular Mrnas

Simian virus 40-based plasmids that direct the synthesis of preproinsulin in cultured monkey cells were used to study the effects of mRNA structure on translational efficiency. Lengthening the leader sequence enhanced translation in this system. The enhancement was most obvious when an unstructured sequence (two, four, or eight copies of the oligonucleotide AGCTAAGTAAGTAAGTA) was inserted upstream from a region of deliberate secondary structure; the degree of enhancement was proportional to the number of copies of the inserted oligonucleotide. Lengthening the leader sequence on the 3' side of a stem-and-loop structure, in contrast, did not offset the potentially inhibitory effect of the hairpin structure. Both the facilitating effect of length and the inhibitory effect of secondary structure were demonstrated most easily under conditions of mRNA competition, which was brought about by an abrupt shift in the tonicity of the culture medium. These experiments suggest a simple structural basis for the long-recognized differential response of viral and cellular mRNAs to hypertonic stress. The fact that the translatability of structure-prone mRNAs varies with changes in the environment may also have general implications for gene expression in eucaryotic cells.

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