Structure and expression of daf-12: a nuclear hormone receptor with three isoforms that are involved in development and aging in Caenorhabditis elegans.
During Caenorhabditis elegans early larval development environmental conditions promote a cascade of signaling molecules to direct growth to the reproductive adult or to arrest development as a dauer larva. Two parallel chemosensory signal transduction pathways, one of which is transforming growth factor (TGF)-beta-like, converge on the daf-12 gene to regulate dauer formation. A third insulin-like signaling pathway interacts with the daf-12 pathway to regulate both dauer formation and adult longevity. To further understand the role of daf-12 in these processes, we have molecularly characterized this gene. We establish rescue of the mutant dauer defective phenotype with a genomic clone. We show that three transcripts of different lengths, due to differential splicing, are made from the daf-12 gene. The deduced protein isoforms are similar to both DNA- and ligand-binding domains of nuclear hormone receptors. The three daf-12 transcripts are produced throughout development and expression increases during the preparation for and execution of dauer formation. Analysis of various daf mutant strains suggests that the isoform ratios of daf-12 steady-state mRNA are not changed by reduction of function in the TGF-beta and insulin signaling components of the dauer pathway. The daf-12 promoter directs expression of GFP in the pharynx. daf-12 is a C. elegans nuclear hormone receptor with multiple isoforms, is expressed throughout development in distinct cells, and functions under a variety of environmental conditions.
Snow
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MI
Molecular Biology Program and Division of Biogerontology, University of Southern California, Los Angeles, CA 90089, USA.
Larsen
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PL
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D003360:Cosmids / Q000235:genetics; D005091:Exons / Q000235:genetics; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins; D007328:Insulin / Q000494:pharmacology; D007438:Introns / Q000235:genetics; D007814:Larva / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010614:Pharynx / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014170:Transformation, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D007328:Insulin; D008164:Luminescent Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins