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Coordination of iron and oxygen sensing through post‐transcriptional regulation of EPAS1
Author(s) -
Davis McKale Raye,
Rendina Elizabeth,
Lucas Edralin A.,
Smith Brenda J.,
Clarke Stephen L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.607.14
Subject(s) - iron deficiency , ferritin , biology , aconitase , post translational regulation , messenger rna , translational regulation , ferroportin , oxygen transport , transcription factor , translation (biology) , microbiology and biotechnology , reactive oxygen species , metabolism , iron homeostasis , biochemistry , chemistry , phosphorylation , anemia , medicine , oxygen , gene , enzyme , organic chemistry
Iron deficiency remains the most common micronutrient deficiency in the US. Diminished erythropoiesis and hemoglobin production as a result of iron deficiency are associated with impaired oxygen transport. Iron homeostasis is maintained through the action of Iron Regulatory Proteins (IRPs) which modulate the stability or translation of mRNAs encoding proteins of iron metabolism. Other mRNAs not intimately involved in cellular iron metabolism have also been described as targets of IRPs. One target, EPAS1, encodes an oxygen‐sensitive transcription factor involved in the maintenance of cellular oxygen homeostasis. The focus of the current study was to examine the extent to which iron status contributes to the translational regulation of EPAS1 mRNA. Using a weanling rat model of iron deficiency, we assessed translational regulation of IRP target mRNAs in the liver by determining the polysomal distribution of target mRNAs. Approximately 50% of EPAS1 mRNA was located in a repressed pool of mRNA in response to iron deficiency. Similarly, ~86% of L‐Ferritin mRNA, a canonical target of IRP, was located in a repressed pool in iron deficient animals. Our results suggest a role for IRPs in regulating EPAS1 translation in response to iron status and provide evidence for coordination of iron and oxygen sensing in response to a dietary iron deficiency. This work was supported by a grant from USDA/CSREES 2008‐35200‐04445 (SLC). Grant Funding Source : USDA/CSREES 2008‐35200‐04445