scholarly journals Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates

2018 ◽  
Author(s):  
Andrea Riba ◽  
Noemi Di Nanni ◽  
Nitish Mittal ◽  
Erik Arhné ◽  
Alexander Schmidt ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Elongation Rate ◽  
Translation Elongation ◽  
Lower Protein ◽  
Protein Output

AbstractAlthough protein synthesis dynamics has been studied both with theoretical models and by profiling ribosome footprints, the determinants of ribosome flux along open reading frames (ORFs) are not fully understood. Combining measurements of protein synthesis rate with ribosome footprinting data, we here inferred translation initiation and elongation rates for over a thousand ORFs in exponentially-growing wildtype yeast cells. We found that the amino acid composition of synthesized proteins is as important a determinant of translation elongation rate as parameters related to codon and tRNA adaptation. We did not find evidence of ribosome collisions curbing the protein output of yeast transcripts, either in high translation conditions associated with exponential growth, or in strains in which deletion of individual ribosomal protein genes leads to globally increased or decreased translation. Slow translation elongation is characteristic of RP-encoding transcripts, which have markedly lower protein output than other transcripts with equally high ribosome densities.Significance StatementAlthough sequencing of ribosome footprints has uncovered new aspects of mRNA translation, the determinants of ribosome flux remain incompletely understood. Combining ribosome footprint data with measurements of protein synthesis rates, we here inferred translation initiation and elongation rates for over a thousand ORFs in yeast strains with varying translation capacity. We found that the translation elongation rate varies up to ~20-fold among yeast transcripts, and is significantly correlated with the rate of translation initiation. Furthermore, the amino acid composition of synthesized proteins impacts the rate of translation elongation to the same extent as measures of codon and tRNA adaptation. Transcripts encoding ribosomal proteins are translated especially slow, having markedly lower protein output than other transcripts with equally high ribosome densities.

scholarly journals Inferring efficiency of translation initiation and elongation from ribosome profiling

2020 ◽  
Vol 48 (17) ◽  
pp. 9478-9490
Author(s):  
Juraj Szavits-Nossan ◽  
Luca Ciandrini
Keyword(s):  
Protein Synthesis ◽  
Mathematical Modelling ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Elongation Rate ◽  
Ribosome Profiling ◽  
Translation Elongation ◽  
Recent Advances ◽  
Two Stages

Abstract One of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation elongation kinetics from ribosome profiling data using recent advances in mathematical modelling of mRNA translation. Our method distinguishes between the elongation rate intrinsic to the ribosome’s stepping cycle and the actual elongation rate that takes into account ribosome interference. This distinction allows us to quantify the extent of ribosomal collisions along the transcript and identify individual codons where ribosomal collisions are likely. When examining ribosome profiling in yeast, we observe that translation initiation and elongation are close to their optima and traffic is minimized at the beginning of the transcript to favour ribosome recruitment. However, we find many individual sites of congestion along the mRNAs where the probability of ribosome interference can reach $50\%$. Our work provides new measures of translation initiation and elongation efficiencies, emphasizing the importance of rating these two stages of translation separately.

scholarly journals Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Francesca Rapino ◽  
Zhaoli Zhou ◽  
Ana Maria Roncero Sanchez ◽  
Marc Joiret ◽  
Christian Seca ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Expression ◽  
Protein Aggregation ◽  
Critical Role ◽  
Mrna Translation ◽  
Trna Modification ◽  
Translation Elongation ◽  
Hydrophilic Amino Acid ◽  
Protein Output

AbstractRegulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm5s2 wobble uridine tRNA modification (U34-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U34-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U34-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis.

scholarly journals Inferring efficiency of translation initiation and elongation from ribosome profiling

2019 ◽  
Author(s):  
Juraj Szavits-Nossan ◽  
Luca Ciandrini
Keyword(s):  
Protein Synthesis ◽  
Mathematical Modelling ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Elongation Rate ◽  
Ribosome Profiling ◽  
Translation Elongation ◽  
Recent Advances ◽  
Two Stages

ABSTRACTOne of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation elongation kinetics from ribosome profiling data using recent advances in the mathematical modelling of mRNA translation. Our method distinguishes between the elongation rate intrinsic to the ribosome’s stepping cycle and the actual elongation rate that takes into account ribosome interference. This distinction allows us to quantify the extent of ribosomal collisions along the transcript and identify individual codons where ribosomal collisions are likely. When examining ribosome profiling in yeast, we observe that translation initiation and elongation are close to their optima, and traffic is minimised at the beginning of the transcript to favour ribosome recruitment. However, we find many individual sites of congestion along the mRNAs where the probability of ribosome interference can reach 50%. Our work provides new measures of translation initiation and elongation efficiencies, emphasising the importance of rating these two stages of translation separately.

scholarly journals A Complementary Mechanism of Bacterial mRNA Translation Inhibition by Tetracyclines

2021 ◽  
Vol 12 ◽  
Author(s):  
Victor Barrenechea ◽  
Maryhory Vargas-Reyes ◽  
Miguel Quiliano ◽  
Pohl Milón
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Ribosomal Subunit ◽  
Mrna Translation ◽  
Resistance Mechanisms ◽  
Dissociation Rate ◽  
Initiation Factor ◽  
Translation Elongation ◽  
Initiation Phase ◽  
Complementary Mechanism

Tetracycline has positively impacted human health as well as the farming and animal industries. Its extensive usage and versatility led to the spread of resistance mechanisms followed by the development of new variants of the antibiotic. Tetracyclines inhibit bacterial growth by impeding the binding of elongator tRNAs to the ribosome. However, a small number of reports indicated that Tetracyclines could also inhibit translation initiation, yet the molecular mechanism remained unknown. Here, we use biochemical and computational methods to study how Oxytetracycline (Otc), Demeclocycline (Dem), and Tigecycline (Tig) affect the translation initiation phase of protein synthesis. Our results show that all three Tetracyclines induce Initiation Factor IF3 to adopt a compact conformation on the 30S ribosomal subunit, similar to that induced by Initiation Factor IF1. This compaction was faster for Tig than Dem or Otc. Furthermore, all three tested tetracyclines affected IF1-bound 30S complexes. The dissociation rate constant of IF1 in early 30S complexes was 14-fold slower for Tig than Dem or Otc. Late 30S initiation complexes (30S pre-IC or IC) exhibited greater IF1 stabilization by Tig than for Dem and Otc. Tig and Otc delayed 50S joining to 30S initiation complexes (30S ICs). Remarkably, the presence of Tig considerably slowed the progression to translation elongation and retained IF1 in the resulting 70S initiation complex (70S IC). Molecular modeling of Tetracyclines bound to the 30S pre-IC and 30S IC indicated that the antibiotics binding site topography fluctuates along the initiation pathway. Mainly, 30S complexes show potential contacts between Dem or Tig with IF1, providing a structural rationale for the enhanced affinity of the antibiotics in the presence of the factor. Altogether, our data indicate that Tetracyclines inhibit translation initiation by allosterically perturbing the IF3 layout on the 30S, retaining IF1 during 70S IC formation, and slowing the transition toward translation elongation. Thus, this study describes a new complementary mechanism by which Tetracyclines may inhibit bacterial protein synthesis.

A note on the amino acid composition of sow's milk

1993 ◽  
Vol 57 (03) ◽  
pp. 500-502
Author(s):  
R. H. King ◽  
C. J. Rayner ◽  
M. Kerr
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Dietary Protein ◽  
Crude Protein ◽  
Protein Concentration ◽  
Milk Protein ◽  
Lactating Sows ◽  
Protein Output

Effects of dietary protein concentration on the amino acid composition of sow's milk was studied using 10 crossbred first-litter sows. At parturition, diets containing similar concentrations of digestible energy but with either 63 or 238 g crude protein per kg and 4.4 and 15.1 g lysine per kg respectively, were given through lactation (five sows per treatment). The ratios of other amino acids to lysine were in excess of those currently recommended for lactating sows. Dietary protein level significantly affected milk yield, gave higher milk protein output (P> 0.05) but was without significant effect on the proportions of amino acids in the milk.

scholarly journals Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice

Amino Acids ◽  
2011 ◽  
Vol 42 (6) ◽  
pp. 2481-2489 ◽  
Author(s):  
Hitoshi Murakami ◽  
Kazutaka Shimbo ◽  
Yoshiko Inoue ◽  
Yoshinobu Takino ◽  
Hisamine Kobayashi
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Collagen Protein ◽  
Skin Collagen

Prey amino acid composition affects rates of protein synthesis and N wastage of a freshwater carnivore

2020 ◽  
Vol 71 (2) ◽  
pp. 229 ◽  
Author(s):  
Georgia K. Dwyer ◽  
Rick J. Stoffels ◽  
Ewen Silvester ◽  
Gavin N. Rees
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Energy Production ◽  
Ammonia Excretion ◽  
Specific Dynamic Action ◽  
Fish Diet ◽  
Dietary Amino Acids ◽  
Ideal Protein

Humans modify prey communities and hence alter the availability of nutrients to wild carnivores. Such changes in amino acid ‘landscapes’ are likely to affect the growth of individuals, and potentially the success of populations. This study aimed to determine whether amino acid composition of animal prey alone affects protein synthesis efficiency and N wastage of a freshwater carnivore. River blackfish (Gadopsis marmoratus) were fed two diets differing only in amino acid composition: the first diet was formulated to match the composition of the fish themselves, representing a balanced ‘ideal protein’, whereas the second diet was produced to match the composition of a prey item, namely the shrimp Macrobrachium australiense. By measuring the postprandial increase in metabolic rate (specific dynamic action) and ammonia excretion, it was found that the amino acid composition of the fish diet was associated with an increase in protein synthesis, whereas the shrimp diet doubled the amount of dietary amino acids directed to pathways of catabolic energy production and N wastage. This study adds to the stoichiometric ecology literature by showing that changes in the amino acid composition of food webs could affect carnivore growth and nutrient cycling.

scholarly journals Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates

2019 ◽  
Vol 116 (30) ◽  
pp. 15023-15032 ◽  
Author(s):  
Andrea Riba ◽  
Noemi Di Nanni ◽  
Nitish Mittal ◽  
Erik Arhné ◽  
Alexander Schmidt ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Theoretical Models ◽  
Open Reading Frames ◽  
Yeast Cells ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Translation Elongation ◽  
Lower Protein ◽  
Ribosome Footprinting ◽  
Protein Output

Although protein synthesis dynamics has been studied both with theoretical models and by profiling ribosome footprints, the determinants of ribosome flux along open reading frames (ORFs) are not fully understood. Combining measurements of protein synthesis rate with ribosome footprinting data, we here inferred translation initiation and elongation rates for over a 1,000 ORFs in exponentially growing wild-type yeast cells. We found that the amino acid composition of synthesized proteins is as important a determinant of translation elongation rate as parameters related to codon and transfer RNA (tRNA) adaptation. We did not find evidence of ribosome collisions curbing the protein output of yeast transcripts, either in high translation conditions associated with exponential growth, or in strains in which deletion of individual ribosomal protein (RP) genes leads to globally increased or decreased translation. Slow translation elongation is characteristic of RP-encoding transcripts, which have markedly lower protein output compared with other transcripts with equally high ribosome densities.

scholarly journals The Anabolic Response to Plant-Based Protein Ingestion

2021 ◽  
Author(s):  
Philippe J. M. Pinckaers ◽  
Jorn Trommelen ◽  
Tim Snijders ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Content ◽  
Protein Source ◽  
Protein Sources

AbstractThere is a global trend of an increased interest in plant-based diets. This includes an increase in the consumption of plant-based proteins at the expense of animal-based proteins. Plant-derived proteins are now also frequently applied in sports nutrition. So far, we have learned that the ingestion of plant-derived proteins, such as soy and wheat protein, result in lower post-prandial muscle protein synthesis responses when compared with the ingestion of an equivalent amount of animal-based protein. The lesser anabolic properties of plant-based versus animal-derived proteins may be attributed to differences in their protein digestion and amino acid absorption kinetics, as well as to differences in amino acid composition between these protein sources. Most plant-based proteins have a low essential amino acid content and are often deficient in one or more specific amino acids, such as lysine and methionine. However, there are large differences in amino acid composition between various plant-derived proteins or plant-based protein sources. So far, only a few studies have directly compared the muscle protein synthetic response following the ingestion of a plant-derived protein versus a high(er) quality animal-derived protein. The proposed lower anabolic properties of plant- versus animal-derived proteins may be compensated for by (i) consuming a greater amount of the plant-derived protein or plant-based protein source to compensate for the lesser quality; (ii) using specific blends of plant-based proteins to create a more balanced amino acid profile; (iii) fortifying the plant-based protein (source) with the specific free amino acid(s) that is (are) deficient. Clinical studies are warranted to assess the anabolic properties of the various plant-derived proteins and their protein sources in vivo in humans and to identify the factors that may or may not compromise the capacity to stimulate post-prandial muscle protein synthesis rates. Such work is needed to determine whether the transition towards a more plant-based diet is accompanied by a transition towards greater dietary protein intake requirements.

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