Zhang et al. 2018 (PRJNA488955)

General Details

Title Iron and Heme Coordinate Erythropoiesis through HRI-Mediated Regulation of Protein Translation and Gene Expression
Organism
Number of Samples 8
Release Date 2018/09/02 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP159428
ENA SRP159428
GEO
BioProject PRJNA488955

Publication

Title
Authors Zhang S,Macias-Garcia A,Ulirsch JC,Velazquez J,Butty VL,Levine SS,Sankaran VG,Chen JJ
Journal eLife
Publication Date 2019 Apr 29
Abstract Iron and heme play central roles in the production of red blood cells, but the underlying mechanisms remain incompletely understood. Heme-regulated eIF2α kinase (HRI) controls translation by phosphorylating eIF2α. Here, we investigate the global impact of iron, heme, and HRI on protein translation in vivo in murine primary erythroblasts using ribosome profiling. We validate the known role of HRI-mediated translational stimulation of integratedstressresponse mRNAs during iron deficiency in vivo. Moreover, we find that the translation of mRNAs encoding cytosolic and mitochondrial ribosomal proteins is substantially repressed by HRI during iron deficiency, causing a decrease in cytosolic and mitochondrial protein synthesis. The absence of HRI during iron deficiency elicits a prominent cytoplasmic unfolded protein response and impairs mitochondrial respiration. Importantly, ATF4 target genes are activated during iron deficiency to maintain mitochondrial function and to enable erythroid differentiation. We further identify GRB10 as a previously unappreciated regulator of terminal erythropoiesis. © 2019, Zhang et al.
PMC PMC6533081
PMID 31033440
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR7777908 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777909 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777910 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777911 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777912 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777913 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777914 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
SRR7777915 PRJNA488955 Mus musculus Primary basophilic erythroblasts Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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