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 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.
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.
Eric W
EW
Mills
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jamie
J
Wangen
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ragreen@jhmi.edu.
Rachel
R
Green
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.
Nicholas T
NT
Ingolia
D020413:3' Untranslated Regions; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics*; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004720:Endonucleases; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D014176:Protein Biosynthesis; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism
D020413:3' Untranslated Regions; C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D018840:HSP70 Heat-Shock Proteins; D006454:Hemoglobins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D004720:Endonucleases; C550527:pelo protein, human; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human
Dom34; Pelota; erythropoiesis; reticulocyte; ribosome recycling; ribosome rescue; thrombopoiesis
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