Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells.
Hemoglobin synthesis in red cells is the major iron utilization pathway in the human body and accounts for > 80% of systemic iron turnover. The first step in erythroid heme biosynthesis is catalyzed by a tissue-specific isoform of 5-aminolevulinate synthase (ALAS). The previous identification of iron-responsive elements in the 5'-untranslated region of human and murine erythroid ALAS mRNA raised the intriguing possibility that eALAS expression might be under iron-dependent translational control. As a consequence, a single post-transcriptional regulatory system could coordinate cellular iron acquisition via the transferrin receptor, storage via ferritin, and utilization via eALAS. We directly demonstrate iron-dependent translational regulation of eALAS mRNA in murine erythroleukemia (MEL) cells. The iron-responsive element motif contained in eALAS mRNA is shown to be sufficient to confer translational control to a reporter mRNA both in transfected MEL cells and in vitro.
Melefors
O
O
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Goossen
B
B
Johansson
H E
HE
Stripecke
R
R
Gray
N K
NK
Hentze
M W
MW
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004912:Erythrocytes / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007501:Iron / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D007501:Iron; D000624:5-Aminolevulinate Synthetase