title: Stress granules contribute to α-globin homeostasis in differentiating erythroid cells.
abstract: Hemoglobin is the major biosynthetic product of developing erythroid cells. Assembly of hemoglobin requires the balanced production of globin proteins and the oxygen-carrying heme moiety. The heme-regulated inhibitor kinase (HRI) participates in this process by phosphorylating eIF2α and inhibiting the translation of globin proteins when levels of free heme are limiting. HRI is also activated in erythroid cells subjected to oxidative stress. Phospho-eIF2α-mediated translational repression induces the assembly of stress granules (SG), cytoplasmic foci that harbor untranslated mRNAs and promote the survival of cells subjected to adverse environmental conditions. We have found that differentiating erythroid, but not myelomonocytic or megakaryocytic, murine and human progenitor cells assemble SGs, in vitro and in vivo. Targeted knockdown of HRI or G3BP, a protein required for SG assembly, inhibits spontaneous and arsenite-induced assembly of SGs in erythroid progenitor cells. This is accompanied by reduced α-globin production and increased apoptosis suggesting that G3BP+ SGs facilitate the survival of developing erythroid cells.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, One Jimmy Fund Way, Smith 652, Boston, MA 02115, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Ghisolfi
authors.forename: Shilpee
authors.initials: S
authors.lastname: Dutt
authors.forename: Marie E
authors.initials: ME
authors.lastname: McConkey
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.forename: Paul
authors.initials: P
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000502:physiology*; D004265:DNA Helicases; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D004920:Erythropoiesis; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D014158:Transcription, Genetic; D055542:alpha-Globins / Q000096:biosynthesis* / Q000235:genetics; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D055542:alpha-Globins; D019892:eIF-2 Kinase; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases