Pairs of amino acids at the P- and A-sites of the ribosome predictably and causally modulate translation-elongation rates
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ABSTRACT:
PROVIDER: PRJNA551280 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9602850.fastq.gz | Fastqsanger.gz | |||
| SRR9602860.fastq.gz | Fastqsanger.gz | |||
| SRR9602870.fastq.gz | Fastqsanger.gz | |||
| SRR9602880.fastq.gz | Fastqsanger.gz | |||
| SRR9602890.fastq.gz | Fastqsanger.gz |
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Project description:Variation in translation-elongation kinetics along a transcript’s coding sequence plays an important role in the maintenance of cellular protein homeostasis by regulating co-translational protein folding, localization, and maturation. Translation-elongation speed is influenced by molecular factors within mRNA and protein sequences. For example, when proline is present in the ribosome’s P- or A-site translation slows down, but the effect of other pairs of amino acids, in the context of all 400 possible pairs, has not been characterized. Here, we study Saccharomyces cerevisiae using a combination of mutational experiments, bioinformatics, and evolutionary analyses, and show that many different pairs of amino acids and their associated tRNA molecules predictably and causally encode translation rate information when these pairs are present in the A- and P-sites of the ribosome independent of other factors known to influence translation speed, including mRNA structure, wobble base pairing, tripeptide motifs, positively charged upstream nascent chain residues, and cognate tRNA concentration. The fast-translating pairs of amino acids that we identify are enriched seven-fold relative to the slow-translating pairs across Saccharomyces cerevisiae’s proteome, while the slow-translating pairs are enriched downstream of domain boundaries. Thus, the chemical identity of amino acid pairs contributes to variability in translation rates, elongation kinetics are causally encoded in the primary structure of proteins, and signatures of evolutionary selection indicate their potential role in co-translational processes.
2020-04-20 | GSE133370 | GEO
Project description:Variation in translation-elongation kinetics along a transcript's coding sequence plays an important role in the maintenance of cellular protein homeostasis by regulating co-translational protein folding, localization, and maturation. Translation-elongation speed is influenced by molecular factors within mRNA and protein sequences. For example, the presence of proline in the ribosome's P- or A-site slows down translation, but the effect of other pairs of amino acids, in the context of all 400 possible pairs, has not been characterized. Here, we study Saccharomyces cerevisiae using a combination of bioinformatics, mutational experiments, and evolutionary analyses, and show that many different pairs of amino acids and their associated tRNA molecules predictably and causally encode translation rate information when these pairs are present in the A- and P-sites of the ribosome independent of other factors known to influence translation speed including mRNA structure, wobble base pairing, tripeptide motifs, positively charged upstream nascent chain residues, and cognate tRNA concentration. The fast-translating pairs of amino acids that we identify are enriched four-fold relative to the slow-translating pairs across Saccharomyces cerevisiae's proteome, while the slow-translating pairs are enriched downstream of domain boundaries. Thus, the chemical identity of amino acid pairs contributes to variability in translation rates, elongation kinetics are causally encoded in the primary structure of proteins, and signatures of evolutionary selection indicate their potential role in co-translational processes.
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Project description:D-amino acids enrichment Raw sequence reads
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Project description:Messenger RNA (mRNA) translation can lead to higher rates of mRNA decay, suggesting a role for the ribosome in mRNA destruction. Furthermore, features of an mRNA, such as codon identities, that are directly probed by the ribosome also correlate with mRNA decay rates. Specifically, many amino acids are encoded by synonymous codons, and some synonymous codons are decoded by more abundant tRNAs leading to more optimal translation and increased mRNA stability. In addition to different translation rates, the presence of individual codons can lead to higher or lower rates of amino acid misincorporation which could potentially lead to protein misfolding if an individual amino acid makes many critical contacts in a structure. Here, we directly test whether amino acid misincorporation affects mRNA stability, taking advantage of an aminoglycoside antibiotic (G418) which promotes higher error rates in the ribosome. We observe that G418 decreases firefly luciferase mRNA stability in an in vitro system, and we similarly observe that G418 reduces mRNA stability in mouse embryonic stem cells (mESCs). G418-sensitive mRNAs are enriched for suboptimal hydrophobic amino acid codons as well as other codons that are known to result in higher rates of amino acid misincorporation. Since protein folding is highly sensitive to the identity of hydrophobic amino acids, these results strongly suggest that defects in protein folding are linked to mRNA decay.
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2011-01-11 | E-GEOD-26536 | biostudies-arrayexpress
Project description:Electrostatic potentials along the ribosomal exit tunnel are nonuniform and negative. The significance of electrostatics in the tunnel remains relatively uninvestigated, yet they are likely to play a role in translation and secondary folding of nascent peptides. To probe the role of nascent peptide charges in ribosome function, we used a molecular tape measure that was engineered to contain different numbers of charged amino acids localized to known regions of the tunnel and measured chain elongation rates. Positively charged arginine or lysine sequences produce transient arrest (pausing) before the nascent peptide is fully elongated. The rate of conversion from transiently arrested to full-length nascent peptide is faster for peptides containing neutral or negatively charged residues than for those containing positively charged residues. We provide experimental evidence that extraribosomal mechanisms do not account for this charge-specific pausing. We conclude that pausing is due to charge-specific interactions between the tunnel and the nascent peptide.
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Project description: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 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 compared to other transcripts with equally high ribosome densities.
2019-09-10 | PXD014357 | Pride
Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery.
There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.
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Project description:The aim of this work was to analyze the transcriptomic response of Buchnera aphidicola when the aphid host is submitted to depletion in essential amino acids (EAA). This treatment was combined with an increase in sucrose concentration to influence the bacterial growth rate. In this experiment, the dietary amino acids had an EAA:nonEAA ratio of either 1:1 (50% EAA) or 1:3 (25% EAA), giving low and high aphid demand of Buchnera-derived essential amino acids, respectively. This comparison was set in a 2 times 2 factorial design with sucrose concentration at 0.5 M and 1.0 M, supporting high and low aphid growth rates.
2006-04-03 | E-TABM-85 | biostudies-arrayexpress
Project description:Transcription is regulated at multiple levels, including initiation, elongation, and termination. Whereas much research has focused on initiation of transcription, regulation of elongation plays an important role not only for transcription dynamics, but also for co-transcriptional RNA processing as the RNAPII elongation rate can influence maturation of the nascent RNA transcript. Despite advances in high-throughput approaches for global identification of RNAPII speed, RNAPII elongation rate studies have been largely limited to a small number of genes. Here, we present DRB/TTchem-seq2, a modified version of DRB/TTchem-seq method, to measure gene-specific elongation rates of more than 3,000 genes. By approximating the distance traveled by RNAPII in certain time intervals using the wave fronts post RNAPII release. Our direct RNAPII elongation rate quantification reveals that elongation rates vary not only among genes but also within genes. Additionally, specific histone modifications and elongation factors are tightly correlated with the elongation rates. Together, we present a robust and powerful method for RNAPII transcription elongation rate measurement.
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