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RNA-Seq of purified P-bodies from HEK293 cells

ABSTRACT: RNA-Seq of purified P-bodies from HEK293 cells

PROVIDER: PRJEB19388 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR1824640.fastq.gz	Fastqsanger.gz
	ERR1824641.fastq.gz	Fastqsanger.gz
	ERR1824642.fastq.gz	Fastqsanger.gz
	ERR1824637.fastq.gz	Fastqsanger.gz
	ERR1824638.fastq.gz	Fastqsanger.gz

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RNA-Seq of purified P-bodies from HEK293 cells

Project description:To identify RNAs accumulating in P-bodies (cytoslic RNP granules), P-bodies were purified from HEK293 cell extracts using a Flow Activated Particle Sorting (FAPS) method. Sorted P-bodies were compared to the pre-sorted fraction to identify RNA enriched in P-bodies.

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Project description:Post-transcriptional mechanisms are fundamental safeguards of progenitor cell identity and are often dysregulated in cancer. Here, we identified regulators of P-bodies as crucial vulnerabilities in acute myeloid leukaemia (AML) through genome-wide CRISPR screens in normal and malignant haematopoietic progenitors. We found that leukaemia cells harbour aberrantly elevated numbers of P-bodies and show that P-body assembly is crucial for initiation and maintenance of AML. Notably, P-body loss had little effect upon homoeostatic haematopoiesis but impacted regenerative haematopoiesis. Molecular characterization of P-bodies purified from human AML cells unveiled their critical role in sequestering messenger RNAs encoding potent tumour suppressors from the translational machinery. P-body dissolution promoted translation of these mRNAs, which in turn rewired gene expression and chromatin architecture in leukaemia cells. Collectively, our findings highlight the contrasting and unique roles of RNA sequestration in P-bodies during tissue homoeostasis and oncogenesis. These insights open potential avenues for understanding myeloid leukaemia and potential therapeutic interventions.

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