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Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα

ABSTRACT: Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα

PROVIDER: PRJNA940166 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23680515.fastq.gz	Fastqsanger.gz
	SRR23680516.fastq.gz	Fastqsanger.gz
	SRR23680517.fastq.gz	Fastqsanger.gz
	SRR23680518.fastq.gz	Fastqsanger.gz
	SRR23680519.fastq.gz	Fastqsanger.gz

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Similar Datasets

Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [CRISPRi]

Project description:Translation initiation at alternative start sites can dynamically control the synthesis of two or more functionally distinct protein isoforms from a single mRNA. Alternate isoforms of the hematopoietic transcription factor C/EBPα produced from different start sites exert opposing effects during myeloid cell development. This alternative initiation depends on sequence features of the CEBPA transcript, including a regulatory upstream open reading frame (uORF), but the molecular basis is not fully understood. Here we identify trans-acting factors that affect C/EBPα isoform choice using a sensitive and quantitative two-color fluorescence reporter coupled with CRISPRi screening. Our screen uncovered a role for the ribosome rescue factor PELOTA (PELO) in promoting expression of the longer C/EBPα isoform, by directly removing inhibitory unrecycled ribosomes and through indirect effects mediated by the mechanistic target of rapamycin (mTOR) kinase. Our work provides further mechanistic insights into coupling between ribosome recycling and translation reinitiation in regulation of a key transcription factor, with implications for normal hematopoiesis and leukemiagenesis.

2023-03-08 | GSE226435 | GEO

Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [riboprofiling]

2023-03-08 | GSE226436 | GEO

Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [riboprofiling]

Project description:Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [riboprofiling]

| PRJNA940173 | ENA

Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [CRISPRi]

Project description:Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα [CRISPRi]

| PRJNA940170 | ENA

Ribosome rescue factor PELOTA modulates translation start site choice and protein isoform levels of transcription factor C/EBPα

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-08 | GSE226437 | GEO

Genome-wide co-occupancy of Hoxa9 and C/EBPα in Hoxa9/Meis1 transformed HSCs [ChIP-seq]

Project description:Identification of the genome-wide binding sites of Hoxa9 and C/EBPα in a murine myeloblastic cell line transformed by Hoxa9/Meis1. Over 50% of Hoxa9 binding sites are co-bound by C/EBPα, providing mechanistic insight into the requirement of C/EBPα for Hoxa9-mediated leukemogenesis. Additionally, genome-wide occupancy of H3K4 monomethylation and H3K27 trimethylation provide additional information on the functionality of Hoxa9/C/EBPα cobound loci. Examination of two transcription factor binding sites and two histone modifications in a transformed cell line.

2014-06-11 | E-GEOD-58361 | biostudies-arrayexpress

Temporal mapping of C/EBPα and –β binding during liver regeneration

Project description:Temporal mapping of C/EBPα and –β binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries. Timeseries ChIP-seq of transcription factors C/EBPα and –β, and Pol II in time points 0, 3, 8, 16, 24, 36, 48, 168 hours after partial hepatectomy. Additionally, an IgG mock to 0h was sequenced, as well as the transcription factor Egr1.

2013-01-24 | E-GEOD-42321 | biostudies-arrayexpress

Development of MLL-rearranged leukemia is dependent on a transcriptional program orchestradt by C/EBPα

Project description:Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBPα to be up-regulated in the AML samples, suggesting that C/EBPα might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBPα activity both in early progenitors as well as in GMPs. In contrast, C/EBPα was found to be indispensable in an already established leukemia. These results suggest that C/EBPα play an important role in the early transforming event of leukemogenesis. We used microarray to study the early transcriptional changes induced by MLL-ENL expression and we identified a combined C/EBPα / MLL-ENL transcriptional signature. 3 Cebpaflox/flox;Mx1Cre and 3 Cebpaflox/flox;Mx1Cre- mice were sacrificed 14 days after pIpC injection and bone marrow cells were harvested, enriched for cKit-expression and transduced with a pMIG retroviral vector expressing the MLL-ENL fusion protein and GFP. 72 h post first transduction, GFP-positive or negative PreGM cells were sorted.

2013-12-10 | E-GEOD-46534 | biostudies-arrayexpress

C/EBPα and PPARγ-specific transcriptional programs in mature adipocytes in vivo

Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBPα in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBPα, as a lipogenic transcription factor, has unique direct targets compared to PPARγ. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBPα and PPARγ in adipocytes by short-term C/EBPα or PPARγ elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBPα and PPARγ cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBPα specific targets in mice on a chow diet, most of the C/EBPα targets in mature adipocytes are genes modulated by HFD feeding.

2014-11-04 | GSE62937 | GEO

Sox4 is a key oncogenic target in C/EBPα mutant Acute Myeloid Leukemia

Project description:Mutation or epigenetic silencing of the transcription factor C/EBPα is observed in ~10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but down-stream targets relevant for leukemogenesis are not known. Here we identify Sox4 as a direct target of C/EBPα whereby its expression is inversely correlated with C/EBPα activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia initiating cells (LICs) from both Sox4 overexpression and murine mutant C/EBPα AML models clustered together, but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBPα inactivation contributes to the development of leukemias with a distinct LIC phenotype.

2013-03-23 | GSE45430 | GEO

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