Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets
Protein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from anucleate lineages by ribosome profiling and uncover a dramatic accumulation of post-termination...
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doaj-ba041826ab964115997d6bb5cbb0816f2020-11-24T21:47:27ZengElsevierCell Reports2211-12472016-09-0117111010.1016/j.celrep.2016.08.088Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and PlateletsEric W. Mills0Jamie Wangen1Rachel Green2Nicholas T. Ingolia3Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Embryology, Carnegie Institution of Washington, Baltimore, MD 21218, USAProtein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from anucleate lineages by ribosome profiling and uncover a dramatic accumulation of post-termination unrecycled ribosomes in the 3′ UTRs of mRNAs. We demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation. Induction of the ribosome rescue factors PELO and HBS1L is required to support protein synthesis when ABCE1 levels fall and for hemoglobin production during blood cell development. Our observations suggest that this distinctive loss of ABCE1 in anucleate blood lineages could sensitize them to defects in ribosome homeostasis, perhaps explaining in part why genetic defects in the fundamental process of ribosome production (“ribosomopathies”) often affect hematopoiesis specifically.http://www.sciencedirect.com/science/article/pii/S2211124716311974ribosome recyclingribosome rescuePelotaDom34erythropoiesisthrombopoiesisreticulocyte |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eric W. Mills Jamie Wangen Rachel Green Nicholas T. Ingolia |
spellingShingle |
Eric W. Mills Jamie Wangen Rachel Green Nicholas T. Ingolia Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets Cell Reports ribosome recycling ribosome rescue Pelota Dom34 erythropoiesis thrombopoiesis reticulocyte |
author_facet |
Eric W. Mills Jamie Wangen Rachel Green Nicholas T. Ingolia |
author_sort |
Eric W. Mills |
title |
Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets |
title_short |
Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets |
title_full |
Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets |
title_fullStr |
Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets |
title_full_unstemmed |
Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets |
title_sort |
dynamic regulation of a ribosome rescue pathway in erythroid cells and platelets |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-09-01 |
description |
Protein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from anucleate lineages by ribosome profiling and uncover a dramatic accumulation of post-termination unrecycled ribosomes in the 3′ UTRs of mRNAs. We demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation. Induction of the ribosome rescue factors PELO and HBS1L is required to support protein synthesis when ABCE1 levels fall and for hemoglobin production during blood cell development. Our observations suggest that this distinctive loss of ABCE1 in anucleate blood lineages could sensitize them to defects in ribosome homeostasis, perhaps explaining in part why genetic defects in the fundamental process of ribosome production (“ribosomopathies”) often affect hematopoiesis specifically. |
topic |
ribosome recycling ribosome rescue Pelota Dom34 erythropoiesis thrombopoiesis reticulocyte |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716311974 |
work_keys_str_mv |
AT ericwmills dynamicregulationofaribosomerescuepathwayinerythroidcellsandplatelets AT jamiewangen dynamicregulationofaribosomerescuepathwayinerythroidcellsandplatelets AT rachelgreen dynamicregulationofaribosomerescuepathwayinerythroidcellsandplatelets AT nicholastingolia dynamicregulationofaribosomerescuepathwayinerythroidcellsandplatelets |
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