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Proteome changes in PTBP1 deficient hematopoietic cells

ABSTRACT: Ribosomopathies constitute a range of disabling conditions associated with defective protein synthesis mainly affecting hematopoietic stem cells (HSCs) and erythroid development. Here we demonstrate that deletion of Polypyrimidine Tract Binding Protein 1 (PTBP1) in the hematopoietic compartment led to the development of a ribosomopathy-like condition. Specifically, loss of PTBP1 was associated with a decrease in HSC self-renewal, erythroid differentiation and protein synthesis. Consistent with its function as a splicing regulator, PTBP1 deficiency led to splicing defects in hundreds of genes and we demonstrate that the up-regulation of a specific isoform of CDC42 could partly mimic the protein synthesis defect associated with loss of PTBP1. Furthermore, PTBP1 deficiency was associated with a marked defect in ribosome biogenesis and a selective reduction in the translation of mRNAs encoding ribosomal proteins. Collectively, this work identifies PTBP1 as a key integrator of ribosomal functions and highlights the broad functional repertoire of RNA binding proteins.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow

SUBMITTER: Erwin Schoof

LAB HEAD: Bo Porse

PROVIDER: PXD023879 | Pride | 2022-05-04

REPOSITORIES: Pride

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			Action	DRS
	20161205_FS_EMS_MRE_preMegE_KO_1_1.raw	Raw
	20161205_FS_EMS_MRE_preMegE_KO_1_2.raw	Raw
	20161205_FS_EMS_MRE_preMegE_KO_1_X.raw	Raw
	20161205_FS_EMS_MRE_preMegE_KO_2_1.raw	Raw
	20161205_FS_EMS_MRE_preMegE_KO_2_2.raw	Raw

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Project description:Ribosomopathies constitute a range of disorders associated with defective protein synthesis mainly affecting hematopoietic stem cells (HSCs) and erythroid development. Here we demonstrate that deletion of Polypyrimidine Tract Binding Protein 1 (PTBP1) in the hematopoietic compartment led to the development of a ribosomopathy-like condition. Specifically, loss of PTBP1 was associated with decreases in HSC self-renewal, erythroid differentiation and protein synthesis. Consistent with its function as a splicing regulator, PTBP1 deficiency led to splicing defects in hundreds of genes, and we demonstrate that the up-regulation of a specific isoform of CDC42 could partly mimic the protein synthesis defect associated with loss of PTBP1. Furthermore, PTBP1 deficiency was associated with a marked defect in ribosome biogenesis and a selective reduction in the translation of mRNAs encoding ribosomal proteins. Collectively, this work identifies PTBP1 as a key integrator of ribosomal functions and highlights the broad functional repertoire of RNA binding proteins.

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