Translation elongation rate varies among organs and decreases with age
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE112223 | GEO | 2018/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Translation elongation rate varies among organs and decreases with age
| PRJNA445295 | ENA
Project description:Ribosome profiling data reports on the distribution of translating ribosomes, at steady-state, with codon-level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation. We test whether tRNA abundance affects elongation or translation efficiency by changing the tRNA levels through deletion or over expression and measuring the ribosomal dwell time at each codon using a robust statistical method that accounts for flow conservation.
2015-01-05 | E-GEOD-63789 | biostudies-arrayexpress
Project description:Background: Abscisic acid (ABA) regulates various developmental processes and stress responses over both short (i.e. hours or days) and longer (i.e. months or seasons) time frames. To elucidate the transcriptional regulation of early responses of grapevine (Vitis vinifera) responding to ABA, different organs of grape (berries, shoot tips, leaves, roots and cell cultures) were treated with 10 μM (S)-(+)-ABA for 2 h. NimbleGen whole genome microarrays of Vitis vinifera were used to determine the effects of ABA on organ-specific mRNA expression patterns. Results: Transcriptomic analysis revealed 839 genes whose transcript abundances varied significantly in a specific organ in response to ABA treatment. No single gene exhibited the same changes in transcript abundance across all organs in response to ABA. The biochemical pathways affected by ABA were identified using the Cytoscape program with the BiNGO plug-in software. The results indicated that these 839 genes were involved in several biological processes such as flavonoid metabolism, response to reactive oxygen species, response to light, and response to temperature stimulus. ABA affected ion and water transporters, particularly in the root. The protein amino acid phosphorylation process was significantly overrepresented in shoot tips and roots treated with ABA. ABA affected mRNA abundance of genes (CYP707As, UGTs, and PP2Cs) associated with ABA degradation, conjugation, and the ABA signaling pathway. ABA also significantly affected the expression of several transcription factors (e.g. AP2/ERF, MYC/MYB, and bZIP/AREB). The greatest number of significantly differentially expressed genes was observed in the roots followed by cell cultures, leaves, berries, and shoot tips, respectively. Each organ had a unique set of gene responses to ABA. Conclusions: This study examined the short-term effects of ABA on different organs of grapevine. The responses of each organ were unique indicating that ABA signaling varies with the organ. Understanding the ABA responses in an organ-specific manner is crucial to fully understand hormone action and plant responses to water deficit. Shoot tips and berries samples were collected at the University of California, Davis, CA, USA (2010); cell culture samples were sampled at Oregon State University, OR, USA (2010); roots and leaf samples were collected at the University of Nevada, Reno, Reno, NV, USA (2011). Three independent experimental (and biological) replicates were harvested to compare between ABA-treated and untreated samples. Tissue was derived from Vitis vinifera L. cv. Cabernet Sauvignon.
2016-03-01 | E-GEOD-78798 | biostudies-arrayexpress
Project description:A Chemical Kinetic Basis for Measuring Translation Initiation and Elongation Rates from Ribosome Profiling data
| PRJNA478925 | ENA
Project description:Background: Abscisic acid (ABA) regulates various developmental processes and stress responses over both short (i.e. hours or days) and longer (i.e. months or seasons) time frames. To elucidate the transcriptional regulation of early responses of grapevine (Vitis vinifera) responding to ABA, different organs of grape (berries, shoot tips, leaves, roots and cell cultures) were treated with 10 μM (S)-(+)-ABA for 2 h. NimbleGen whole genome microarrays of Vitis vinifera were used to determine the effects of ABA on organ-specific mRNA expression patterns. Results: Transcriptomic analysis revealed 839 genes whose transcript abundances varied significantly in a specific organ in response to ABA treatment. No single gene exhibited the same changes in transcript abundance across all organs in response to ABA. The biochemical pathways affected by ABA were identified using the Cytoscape program with the BiNGO plug-in software. The results indicated that these 839 genes were involved in several biological processes such as flavonoid metabolism, response to reactive oxygen species, response to light, and response to temperature stimulus. ABA affected ion and water transporters, particularly in the root. The protein amino acid phosphorylation process was significantly overrepresented in shoot tips and roots treated with ABA. ABA affected mRNA abundance of genes (CYP707As, UGTs, and PP2Cs) associated with ABA degradation, conjugation, and the ABA signaling pathway. ABA also significantly affected the expression of several transcription factors (e.g. AP2/ERF, MYC/MYB, and bZIP/AREB). The greatest number of significantly differentially expressed genes was observed in the roots followed by cell cultures, leaves, berries, and shoot tips, respectively. Each organ had a unique set of gene responses to ABA. Conclusions: This study examined the short-term effects of ABA on different organs of grapevine. The responses of each organ were unique indicating that ABA signaling varies with the organ. Understanding the ABA responses in an organ-specific manner is crucial to fully understand hormone action and plant responses to water deficit.
2016-03-01 | GSE78798 | GEO
Project description:Ribosome profiling data reports on the distribution of translating ribosomes, at steady-state, with codon-level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation.
2015-01-05 | GSE63789 | GEO
Project description:Firczuk2013 - Eukaryotic mRNA translation machinery
This is a model of Saccharomyces cerevisiae
mRNA translation which includes the initiation, elongation and termination phases. The model is for 20 condon mRNAs. The building of a multi-factor complex in initiation and also the different processes in elongation and termination are modelled in detail. The model takes into account that ribosomes cover more than one codon of mRNA so that the movement of ribosomes are effectively blocked by other ribosomes several codons downstream. It is assumed that 15 codons are occupied by each ribosome. This blocking effect is considered in reaction R18 in initiation and also reaction R26, the reaction where translocation of ribosomes takes place in elongation. The kinetic functions of these two reactions are based on MacDonald et al. 1968 and Heinrich & Rapaport 1980. All other kinetic functions follow mass-action kinetics. The concentrations of transfer RNA species (Met-tRNA, aa-tRNA and tRNA in the model) are kept constant, while the other species' concentrations can change in the course of the simulation. The model describes the translation of a short mRNA with 20 codons. Therefore, all reactions in the elongation cycle (R22, R23, R25, R26, R28 and R29) and the corresponding species are replicated accordingly to model the species with ribosomes bound at different positions. In summary, the model contains 165 different species and 141 reactions.
The value of the 56 rate constant parameters were estimated by fitting the model against a series of experimental data consisting of modulation of the various translation factors (Figures 2, 3 and S3). Overall the parameter estimation was carried out over 212 different data points (steady states).
This model is described in the article:
An in vivo control map for the eukaryotic mRNA translation machinery
Helena Firczuk, Shichina Kannambath, Jürgen Pahle, Amy Claydon, Robert Beynon, John Duncan, Hans Westerhoff, Pedro Mendes and John EG McCarthy
Molecular Systems Biology. 9:635
Abstract:
Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.
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2024-09-02 | BIOMD0000000457 | BioModels
Project description:Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data. Translation involves molecules and chemical reactions; hence, bioinformatics methods consistent with the laws of chemistry and physics are more likely to produce accurate results. Here, we derive simple equations based on chemical kinetic principles to measure the translation-initiation rate, transcriptome-wide elongation rate, and individual codon translation rates from ribosome profiling experiments. Our methods reproduce the known rates from ribosome profiles generated from detailed simulations of translation. Applying our methods to data from S. cerevisiae and mouse embryonic stem cells we find that the extracted rates reproduce previously reported correlations with various molecular quantities. A codon can exhibit up to 26-fold variability in its translation rate depending upon its context with in a transcript. This broad distribution means that the average translation rate of a codon is not representative of the rate at which most instances of that codon are translated. We also find that mouse embryonic stem cells have a global translation speed that is almost two-fold faster than previously reported. This large variability in translation rates suggests that translational regulation might be used by cells to a greater degree than previously thought.
2018-08-07 | GSE116523 | GEO
Project description:Activation of GCN2 by Ribosome Stalling Links Translation Elongation with Translation Initiation
| PRJNA317428 | ENA
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