Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient
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ABSTRACT:
PROVIDER: PRJNA428737 | ENA |
REPOSITORIES: ENA
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Project description:Ribosomopathies are cell-type-specific pathologies related to a ribosomal protein (RP) gene insult. The 5q- syndrome is a somatic ribosomopathy linked to RPS14 gene haploinsufficiency and characterized by a prominent erythroid hypoplasia. Using quantitative proteomic, we show that GATA1 protein expression is low in shRPS14 cells in which ribosome quantities are diminished. Here, we investigated the cause of low GATA1 protein expression in limiting ribosome availability. A global analysis of translation in RPs deficiencies highlights the rules that drive translation selectivity. We demonstrate that in addition of the transcript length, a high codon adaptation index (CAI) and a highly structured 3’UTR are the key characteristics for a selective translation. An integrated analysis of transcriptome and proteome confirms that the post-transcriptional regulations of gene expression are directly linked to the criteria governing the translational selectivity. In particular, these criteria explain GATA1 translation default with unprecedented precision. More generally, the proteins that accumulate along normal erythropoiesis share the determinants of translation selectivity revealed by the conditions of limiting ribosome availability. We performed translatome expression profiling of cells infected with shRPS14 or shSCR
2020-04-28 | GSE124800 | GEO
Project description:5q- syndrome is a somatic ribosomopathy linked to the monoallelic deletion of the RPS14 gene and characterized by a proeminent erythroid phenotype. The mechanism of anemia involves an impaired differentiation and increased apoptosis of erythroblasts. Here we show that GATA1 protein expression is low in line with a defect in the representation of its mRNA at the ribosome. A global analysis of transcripts on polysomes indicates that translation is selective with a decreased representation of the transcripts with a short coding sequence and UTRs and a highly structured 3’UTR, a subset of transcripts that includes GATA1. Our whole proteome analysis confirms that post-transcriptionally downregulated proteins were encoded by transcripts with a short length and structured 3’UTR. We identified a subset of post-translationally downregulated proteins including ribosomal proteins and translation elongation factors encoded by 5’TOP mRNAs that were enriched on the ribosome. Our results indicate that the thermodynamic characteristics of 3’UTR and in a lesser extend 5’UTR and the transcript length are the determinants of translation selectivity under RPS14 haploinsufficiency conditions and that a post-translational regulation of ribosomal proteins accounts for their decreased content in the cell. We performed transcriptome and translatome expression profiling of cells infected with shRPS14 or shSCR
2020-04-28 | GSE108821 | GEO
Project description:5q- syndrome is a somatic ribosomopathy linked to the monoallelic deletion of the RPS14 gene and characterized by a proeminent erythroid phenotype. The mechanism of anemia involves an impaired differentiation and increased apoptosis of erythroblasts. Here we show that GATA1 protein expression is low in line with a defect in the representation of its mRNA at the ribosome. A global analysis of transcripts on polysomes indicates that translation is selective with a decreased representation of the transcripts with a short coding sequence and UTRs and a highly structured 3’UTR, a subset of transcripts that includes GATA1. Our whole proteome analysis confirms that post-transcriptionally downregulated proteins were encoded by transcripts with a short length and structured 3’UTR. We identified a subset of post-translationally downregulated proteins including ribosomal proteins and translation elongation factors encoded by 5’TOP mRNAs that were enriched on the ribosome. Our results indicate that the thermodynamic characteristics of 3’UTR and in a lesser extend 5’UTR and the transcript length are the determinants of translation selectivity under RPS14 haploinsufficiency conditions and that a post-translational regulation of ribosomal proteins accounts for their decreased content in the cell. We performed transcriptome and translatome expression profiling of cells infected with shRPS14 or shSCR
2020-04-28 | GSE108820 | GEO
Project description:mRNA length and 3’UTR structure govern the translation selectivity in RPS14-haploinsufficient erythroblasts [translatome]
| PRJNA428742 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-28 | GSE108822 | GEO
Project description:Rules governing translation selectivity under limiting ribosome availability
| PRJNA513511 | ENA
Project description:5q- syndrome is a somatic ribosomopathy linked to the monoallelic deletion of the RPS14 gene and characterized by a proeminent erythroid phenotype. The mechanism of anemia involves an impaired differentiation and increased apoptosis of erythroblasts. We have analyzed total cell extracts from UT7 cells with or without a decrease of RPS14 proteins induced by shRNAs. Our data show that GATA1 protein expression is low in line with a defect in the representation of its mRNA at the ribosome. A global analysis of transcripts on polysomes indicates that translation is selective with a decreased representation of the transcripts with a short coding sequence and UTRs and a highly structured 3’UTR, a subset of transcripts that includes GATA1. Our whole proteome analysis confirms that post-transcriptionally downregulated proteins were encoded by transcripts with a short length and structured 3’UTR. We identified a subset of post-translationally downregulated proteins including ribosomal proteins and translation elongation factors encoded by 5’TOP mRNAs that were enriched on the ribosome. Our results indicate that the thermodynamic characteristics of 3’UTR and in a lesser extend 5’UTR and the transcript length are the determinants of translation selectivity under RPS14 haploinsufficiency conditions and that a post-translational regulation of ribosomal proteins accounts for their decreased content in the cell.
2021-04-28 | PXD008650 | Pride
Project description:We performed genome-wide expression profiling of cells infected with control or RPS14 shRNAs. Experiment Overall Design: The purpose of the dataset is to profile analyze the effect of silencing RPS14
2008-11-06 | E-GEOD-9487 | biostudies-arrayexpress
Project description:mRNA length and 3’UTR structure govern the translation selectivity in RPS14-haploinsufficient erythroblasts [transcriptome]
| PRJNA428741 | ENA
Project description:Oocyte-to-embryo transition plays a critical role in oocyte maturation and embryogenesis. It is a highly regulated process in part due to a transcription silenced period followed by zygotic genome activation. How transcriptome, translatome, and proteome interplay in this critical developmental window remains poorly understood. Utilizing a highly sensitive mass spectrometry, we obtained a high-quality proteome landscape spanning 10 stages, from the mouse full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. By integrative analysis with corresponding transcriptome and translatome, we found transcription and translation levels can not reflect protein abundance in most cases. From FGO to 4-cell embryos, proteomes are predominated by FGO-produced proteins, while the transcriptome and translatome are much more dynamic. FGO inherited proteins frequently persist after the corresponding transcripts are already downregulated or decayed. Improved concordance between protein and RNA is observed for genes starting translation only upon meiotic resumption (OET upregulated) or transcribed only in embryos, although the detected protein dynamics often lag behind transcription and translation. Concordance between protein and transcription/tranlation is associated with protein half-lives. Finally, a kinetic model well predicts protein dynamics when incorporating both the initial protein abundance in FGO and translation kinetics across developmental stages. In sum, our study reveals multilayer control of gene expression during oocyte maturation and embryogenesis.
2023-06-06 | GSE209648 | GEO