| First Author | Rehn M | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 6 | Pages | 110793 |
| PubMed ID | 35545054 | Mgi Jnum | J:325087 |
| Mgi Id | MGI:7283990 | Doi | 10.1016/j.celrep.2022.110793 |
| Citation | Rehn M, et al. (2022) PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. Cell Rep 39(6):110793 |
| abstractText | 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. |
