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Cell Rep. 2016 Sep 27;17(1):1-10. doi: 10.1016/j.celrep.2016.08.088.

Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets.

Author information

1
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21218, USA.
2
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ragreen@jhmi.edu.
4
Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21218, USA; Department of Molecular Cell Biology, Center for RNA Systems Biology, Glenn Center for Aging Research, University of California Berkeley, Berkley, CA 94720, USA. Electronic address: ingolia@berkeley.edu.

Abstract

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.

KEYWORDS:

Dom34; Pelota; erythropoiesis; reticulocyte; ribosome recycling; ribosome rescue; thrombopoiesis

PMID:
27681415
PMCID:
PMC5111367
DOI:
10.1016/j.celrep.2016.08.088
[Indexed for MEDLINE]
Free PMC Article

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