Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization.
Iron-sulfur clusters are prosthetic groups that are required for the function of numerous enzymes in the cell, including enzymes important in respiration, photosynthesis, and nitrogen fixation. Here we report cloning of the human homolog of NifS, a cysteine desulfurase that is proposed to supply the inorganic sulfur in iron-sulfur clusters. In human cells, different forms of NifS that localize either to mitochondria or to the cytosol and nucleus are synthesized from a single transcript through initiation at alternative inframe AUGs, and initiation site selection varies according to the pH of the medium or cytosol. Thus, a novel form of translational regulation permits rapid redistribution of NifS proteins into different compartments of the cell in response to changes in metabolic status.
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Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rouault
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D019556:COS Cells; D013437:Carbon-Sulfur Lyases; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology; D018387:Codon, Initiator / Q000235:genetics*; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology; D018628:Gene Dosage; D015870:Gene Expression; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D020014:K562 Cells; D008190:Lyases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D008969:Molecular Sequence Data; D015388:Organelles / Q000737:chemistry / Q000201:enzymology*; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
D018387:Codon, Initiator; D007506:Iron-Sulfur Proteins; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C513492:NFS1 protein, human; C080546:cysteine desulfurase