PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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 poly-pyrimidine-tract-binding protein 1 (PTBP1) in the hematopoietic compartment leads to the development of a ribosomopathy-like condition. Specifically, loss of PTBP1 is associated with decreases in HSC self-renewal, erythroid differentiation, and protein synthesis. Consistent with its function as a splicing regulator, PTBP1 deficiency results in splicing defects in hundreds of genes, and we demonstrate that the up-regulation of a specific isoform of CDC42 partly mimics the protein-synthesis defect associated with loss of PTBP1. Furthermore, PTBP1 deficiency is 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.
Details
Original language | English |
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Article number | 110793 |
Journal | Cell reports |
Volume | 39 |
Issue number | 6 |
Publication status | Published - 10 May 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 35545054 |
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Keywords
ASJC Scopus subject areas
Keywords
- CP: Molecular biology, CP: Stem cell research, hematopoietic stem cells, protein synthesis, PTBP1, red blood cell development, ribosome assembly