PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. / Rehn, Matilda; Wenzel, Anne; Frank, Anne-Katrine; Schuster, Mikkel Bruhn; Pundhir, Sachin; Jørgensen, Nanna; Vitting-Seerup, Kristoffer; Ge, Ying; Jendholm, Johan; Michaut, Magali; Schoof, Erwin M; Jensen, Tanja Lyholm; Rapin, Nicolas; Sapio, Russell T; Andersen, Kasper Langebjerg; Lund, Anders H; Solimena, Michele; Holzenberger, Martin; Pestov, Dimitri G; Porse, Bo Torben.

In: Cell Reports, Vol. 39, No. 6, 110793, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rehn, M, Wenzel, A, Frank, A-K, Schuster, MB, Pundhir, S, Jørgensen, N, Vitting-Seerup, K, Ge, Y, Jendholm, J, Michaut, M, Schoof, EM, Jensen, TL, Rapin, N, Sapio, RT, Andersen, KL, Lund, AH, Solimena, M, Holzenberger, M, Pestov, DG & Porse, BT 2022, 'PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents', Cell Reports, vol. 39, no. 6, 110793. https://doi.org/10.1016/j.celrep.2022.110793

APA

Rehn, M., Wenzel, A., Frank, A-K., Schuster, M. B., Pundhir, S., Jørgensen, N., Vitting-Seerup, K., Ge, Y., Jendholm, J., Michaut, M., Schoof, E. M., Jensen, T. L., Rapin, N., Sapio, R. T., Andersen, K. L., Lund, A. H., Solimena, M., Holzenberger, M., Pestov, D. G., & Porse, B. T. (2022). PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. Cell Reports, 39(6), [110793]. https://doi.org/10.1016/j.celrep.2022.110793

Vancouver

Rehn M, Wenzel A, Frank A-K, Schuster MB, Pundhir S, Jørgensen N et al. PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. Cell Reports. 2022;39(6). 110793. https://doi.org/10.1016/j.celrep.2022.110793

Author

Rehn, Matilda ; Wenzel, Anne ; Frank, Anne-Katrine ; Schuster, Mikkel Bruhn ; Pundhir, Sachin ; Jørgensen, Nanna ; Vitting-Seerup, Kristoffer ; Ge, Ying ; Jendholm, Johan ; Michaut, Magali ; Schoof, Erwin M ; Jensen, Tanja Lyholm ; Rapin, Nicolas ; Sapio, Russell T ; Andersen, Kasper Langebjerg ; Lund, Anders H ; Solimena, Michele ; Holzenberger, Martin ; Pestov, Dimitri G ; Porse, Bo Torben. / PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. In: Cell Reports. 2022 ; Vol. 39, No. 6.

Bibtex

@article{2d9328a4de4648409b590293ee723610,
title = "PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents",
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.",
author = "Matilda Rehn and Anne Wenzel and Anne-Katrine Frank and Schuster, {Mikkel Bruhn} and Sachin Pundhir and Nanna J{\o}rgensen and Kristoffer Vitting-Seerup and Ying Ge and Johan Jendholm and Magali Michaut and Schoof, {Erwin M} and Jensen, {Tanja Lyholm} and Nicolas Rapin and Sapio, {Russell T} and Andersen, {Kasper Langebjerg} and Lund, {Anders H} and Michele Solimena and Martin Holzenberger and Pestov, {Dimitri G} and Porse, {Bo Torben}",
note = "Copyright {\textcopyright} 2022 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2022",
doi = "10.1016/j.celrep.2022.110793",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents

AU - Rehn, Matilda

AU - Wenzel, Anne

AU - Frank, Anne-Katrine

AU - Schuster, Mikkel Bruhn

AU - Pundhir, Sachin

AU - Jørgensen, Nanna

AU - Vitting-Seerup, Kristoffer

AU - Ge, Ying

AU - Jendholm, Johan

AU - Michaut, Magali

AU - Schoof, Erwin M

AU - Jensen, Tanja Lyholm

AU - Rapin, Nicolas

AU - Sapio, Russell T

AU - Andersen, Kasper Langebjerg

AU - Lund, Anders H

AU - Solimena, Michele

AU - Holzenberger, Martin

AU - Pestov, Dimitri G

AU - Porse, Bo Torben

N1 - Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2022.110793

DO - 10.1016/j.celrep.2022.110793

M3 - Journal article

C2 - 35545054

VL - 39

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

M1 - 110793

ER -

ID: 305918898