The global downregulation of protein synthesis observed during hepatogenic differentiation is associated with a decrease in TOP mRNA translation
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PROVIDER: PRJNA723831 | ENA |
REPOSITORIES: ENA
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Project description:Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation both at the global and transcript-specific level. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during the initial exit from pluripotency, but is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the protein abundance of components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepato-specific functions and metabolic maturation are even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring towards hepato-specific transcripts.
2021-04-23 | GSE173106 | GEO
Project description:Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation both at the global and transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency, and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the protein abundance of components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepato-specific functions and metabolic maturation are even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepato-specific transcripts.
2022-12-26 | PXD038204 | Pride
Project description:Downregulation of let-7 by electrical acupuncture increases protein synthesis in mice
| PRJNA736622 | ENA
Project description:In this research we were interested in answering a question whether subjecting Y. lipolytica strain overproducing recombinant secretory protein (rs-Prot) to a specific, pre-optimized stress factor may enhance synthesis of the target macromolecule. Increased osmolarity (3 Osm/kg) was the primary stress factor studied here, implemented alone or in combination with decreased temperature (20C), known to promote synthesis of rs-Prots. The treatments were executed in batch bioreactor cultures, and the cellular reaction was studied in terms of the culture progression, gene expression and global proteomic profiles, to get insight into molecular bases underlying awaken reaction. First of all, we observed that hyperosmolarity executed by high sorbitol concentration does not enhance synthesis of the rs-Prot, but increases its transcription. Expectedly, hyperosmolarity induced synthesis of polyols, at the expense of citric acid and growth, which was severely limited. A number of stress-related genes were upregulated, including several HSPs, AKRs, as observed at transcriptomics and proteomics level. Interestingly, the accompanying concerted downregulation of central carbon metabolism, incl. glycolysis, TCA and fatty acid synthesis, highlighted redirection of carbon fluxes. Elevated abundance of HSPs and osmolytes did not outbalance severe limitation of protein synthesis, marked by orchestrated downregulation of translation (EF-gamma; a number of aa-tRNA synthetases), amino acids biosynthesis and ribosome biogenesis in response to hyperosmolarity. Altogether we ultimately settled that increased osmolarity is not beneficial for rs-Prot synthesis in Y. lipolytica, even though some elements of the response could assist this process. Insight into global changes in the yeast proteome under the treatments is provided.
2021-10-13 | MSV000088228 | MassIVE
Project description:Translation of TOP mRNAs encoding protein synthesis machinery is strictly regulated by an amino acid sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino acid-rich condition, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail length regulation. Consistent with this, tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. Poly(A) tail shortens under mTOR active/ amino acid-rich condition, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino acid-starved (AAS) condition. An RNA-binding protein LARP1 that specifically binds to TOP mRNAs is indispensable for the process. We also show that LARP1 interacts with non-canonical poly(A) polymerases, PAPD4, PAPD5 and PAPD7 and induces post-transcriptional polyadenylation of the target when tethered to the mRNA. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tail under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS.
2022-09-22 | GSE145744 | GEO
Project description:Translation of TOP mRNAs encoding protein synthesis machinery is strictly regulated by an amino acid sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino acid-rich condition, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail length regulation. Consistent with this, tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. Poly(A) tail shortens under mTOR active/ amino acid-rich condition, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino acid-starved (AAS) condition. An RNA-binding protein LARP1 that specifically binds to TOP mRNAs is indispensable for the process. We also show that LARP1 interacts with non-canonical poly(A) polymerases, PAPD4, PAPD5 and PAPD7 and induces post-transcriptional polyadenylation of the target when tethered to the mRNA. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tail under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS.
2022-09-19 | GSE137807 | GEO
Project description:Our previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis. C57/BL6 mice received Acu/LFES treatment on hindlimb for 30 minutes once. Acupuncture points were selected by WHO Standard Acupuncture Nomenclature and electric stimulation applied using an SDZ-II Electronic acupuncture instrument. Muscle protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library in serum exosomes was validated using a High Sensitivity DNA chip. Protein synthesis was enhanced in the both hindlimb and forelimb muscles. Blocking exosome secretion with GW4869 decreased the Acu/LFES-induced increases in protein synthesis. MicroRNA-deep sequencing demonstrated that four members of the Let-7 miRNA family were significantly decreased in serum exosomes. Real time qPCR further verified Acu/LFES-mediated decreases of let-7c-5p in serum exosomes and skeletal muscles. In cultured C2C12 myotubes, inhibition of let-7c not only increased protein synthesis, but also enhanced protein abundance of Igf1, Igf1 receptor. Using a luciferase reporter assay, we demonstrated that let-7 directly inhibits Igf1. Conclusion: Acu/LFES on hindlimb decreases let-7-5p leading to upregulation of the Igf1 signaling and increasing protein synthesis in skeletal muscles. This provides a new understanding of how the electrical acupuncture treatment can positively influence muscle health.
2021-06-11 | GSE176530 | GEO
Project description:La-related protein 1 (LARP1) has been identified as a key translational inhibitor of terminal oligopyrimidine tract (TOP) mRNAs downstream of the nutrient sensing protein kinase complex, mTORC1. LARP1 exerts this inhibitory effect on TOP mRNA translation by binding to the mRNA cap and the adjacent 5’TOP motif, resulting in the displacement of the eIF4E complex from TOP mRNAs. In the present study, we identify a second nutrient sensing kinase GCN2 that converges on LARP1 to control TOP mRNA translation. GCN2 inhibits TOP mRNA translation via ATF4-dependent transcriptional induction of LARP1 mRNAs and GCN1-mediated recruitment of LARP1 to stalled ribosomes. We performed ATF4 ChIP-seq experiments in both WT and GCN2 KO MEFs with or without leucine deprivation.
2022-08-31 | GSE166590 | GEO
Project description:Cucumis melo cultivar:Top Mark Raw sequence reads
| PRJNA358648 | ENA