Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE193912 | GEO | 2023/01/24
REPOSITORIES: GEO
Similar Datasets
Project description:Comparison of overall tRNA level and fraction of charged tRNAs upon treatment with auxin to deplete Not1 in the degron strain and compared to untreated cells.
2023-01-31 | GSE190658 | GEO
Project description:Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
| PRJNA787934 | ENA
Project description:Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
| PRJNA798390 | ENA
Project description:Translation of aberrant or problematic mRNAs can cause ribosome stalling which leads to the production of truncated or defective proteins. Therefore, cells evolved cotranslational quality control mechanisms that eliminate these transcripts and target arrested nascent polypeptides for proteasomal degradation. Here we show that Not4, which is part of the multifunctional Ccr4-Not complex in yeast, associates with polysomes and contributes to the negative regulation of protein synthesis. Not4 is involved in translational repression of transcripts that cause transient ribosome stalling. The absence of Not4 affected global translational repression upon nutrient withdrawal, enhanced the expression of arrested nascent polypeptides and caused constitutive protein folding stress and aggregation. Similar defects were observed in cells with impaired mRNA decapping protein function and in cells lacking the mRNA decapping activator and translational repressor Dhh1. The results suggest a role for Not4 together with components of the decapping machinery in the regulation of protein expression on the mRNA level and emphasize the importance of translational repression for the maintenance of proteome integrity.
| S-EPMC4547895 | biostudies-literature
Project description:The goal is to compare role of Not1,4,5 in co-translational decay from soluble and total RNA pools using null and degron strains
2021-08-18 | GSE168290 | GEO
Project description:Translation of mRNAs is tightly regulated and constantly surveyed for errors. Aberrant translation can trigger co-translational protein and RNA quality control processes, impairments of which cause neurodegeneration by still poorly understood mechanism(s). Here we show that quality control of translation of mitochondrial outer membrane (MOM)-localized mRNA intersects with the turnover of damaged mitochondria, both orchestrated by the mitochondrial kinase PINK1. Mitochondrial damage causes stalled translation of complex-I 30 kDa subunit (C-I30) mRNA on MOM, triggering the recruitment of co-translational quality control factors Pelo, ABCE1, and NOT4 to the ribosome/mRNA-ribonucleoprotein complex. Damage-induced ubiquitination of ABCE1 by NOT4 generates poly-ubiquitin signals that attract autophagy receptors to MOM to initiate mitophagy. In the Drosophila PINK1 model, these factors act synergistically to restore mitophagy and neuromuscular tissue integrity. Thus ribosome-associated co-translational quality control generates an early signal to trigger mitophagy. Our results have broad therapeutic implications for the understanding and treatment of neurodegenerative diseases.
| S-EPMC5989559 | biostudies-literature
Project description:Intracellular levels of deoxyribonucleoside triphosphate (dNTP) must be tightly regulated to preserve genome integrity. Indeed, alterations in dNTP pools have recently been associated with increased mutagenesis, genomic instability and tumorigenesis. However, the mechanisms by which low or imbalanced dNTP pools affect DNA replication remain poorly understood. Here, we have modulated the activity of ribonucleotide reductase (RNR), a key enzyme catalyzing a rate-limiting step of dNTP production, to monitor the effect of altered dNTP levels on replication dynamics in budding yeast. We show that dNTP pools are limiting for normal DNA synthesis as upregulation of RNR activity increases replication fork speed. In contrast, inhibition of RNR activity with hydroxyurea (HU) induces a sharp transition from a regular- to a slow-replication mode within minutes after S-phase entry. Interestingly, we found that upregulation of RNR activity delays this transition and that dNTP levels modulate both fork speed and origin usage under replication stress. Moreover, we report that chromosomal instability (CIN) mutants show increased dNTP pools and enhanced DNA synthesis in the presence of HU. Since upregulation of RNR allows forks to progress faster in the presence of DNA lesions, we propose that CIN mutants adapt to chronic replication stress by upregulating dNTP pools.
2012-01-01 | GSE33686 | GEO
Project description:Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosome density is constant along the length of the mRNA coding region, this can be altered in response to translational regulatory events. In the present study, we developed a method to detect translational regulation of individual mRNAs from their ribosome profiles, utilizing changes in ribosome density. We used mathematical modeling to show that changes in ribosome density should occur along the mRNA at the point of regulation. We analyzed a Ribo-Seq data set obtained for mouse embryonic stem cells and showed that normalization by corresponding RNA-Seq can be used to improve the Ribo-Seq quality by removing bias introduced by deep-sequencing and alignment artifacts. After normalization, we applied a change point algorithm to detect changes in ribosome density present in individual mRNA ribosome profiles. Additional sequence and gene isoform information obtained from the UCSC Genome Browser allowed us to further categorize the detected changes into different mechanisms of regulation. In particular, we detected several mRNAs with known post-transcriptional regulation, e.g., premature termination for selenoprotein mRNAs and translational control of Atf4, but also several more mRNAs with hitherto unknown translational regulation. Additionally, our approach proved useful for identification of new transcript isoforms.
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Project description:Purpose: We aimed to assess the associations of handgrip strength (HS) with cardiovascular and all-cause mortality and whether adding data on HS to cardiovascular disease (CVD) risk factors is associated with improvement in CVD mortality prediction.Design: Handgrip strength was assessed in a population-based sample of 861 participants aged 61-74 years at baseline. Relative HS was obtained by dividing the absolute value by body weight.Results: During a median (interquartile range) follow-up of 17.3 (12.6-18.4) years, 116 fatal coronary heart diseases (CHDs), 195 fatal CVDs and 412 all-cause mortality events occurred. On adjustment for several risk factors, the hazard ratios (95% confidence intervals (CIs)) for fatal CHD, fatal CVD and all-cause mortality were 0.59 (0.37-0.95), 0.59 (0.41-0.86) and 0.66 (0.51-0.84), respectively, comparing extreme tertiles of relative HS. Adding relative HS to a CVD mortality risk prediction model containing established risk factors did not improve discrimination or reclassification using Harrell's C-index (C-index change: 0.0034; p = .65), integrated-discrimination-improvement (0.0059; p = .20) and net-reclassification-improvement (-1.31%; p = .74); however, there was a significant difference in -2 log likelihood (p < .001).Conclusions: Relative HS is inversely associated with CHD, CVD and all-cause mortality events. Adding relative HS to conventional risk factors improves CVD risk assessment using sensitive measures of discrimination.KEY MESSAGESHandgrip strength (HS) assessment is simple, inexpensive and it takes only a few minutes to measure in clinical practice; however, its prognostic role for fatal cardiovascular outcomes on top of traditional risk factors in apparently healthy populations is uncertain.In a population-based prospective cohort study, good HS adjusted for body weight was associated with lower risk of fatal cardiovascular outcomes and the associations remained consistent across several clinically relevant subgroups.Handgrip strength may be a useful prognostic tool for fatal CHD and CVD events, in the general population.
| S-EPMC7877981 | biostudies-literature
Project description:Pools of yeast transcript leaders display differential ribosome recruitment in yeast lysates.
2018-12-01 | GSE98788 | GEO