daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans

Science

Volumn 278, Issue 5341, 1997, Pages 1319-1322

  Lin, Kui ^a   Dorman, Jennie B ^a,b   Rodan, Aylin ^a   Kenyon, Cynthia ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CAENORHABDITIS ELEGANS; CELL DEATH; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE MUTATION; LIFESPAN; NONHUMAN; PRIORITY JOURNAL; SENESCENCE;

AGING; AMINO ACID SEQUENCE; ANIMALS; BASE SEQUENCE; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; CLONING, MOLECULAR; DNA, COMPLEMENTARY; FORKHEAD TRANSCRIPTION FACTORS; GENES, HELMINTH; HUMANS; INSULIN; LONGEVITY; MOLECULAR SEQUENCE DATA; MUTATION; NUCLEAR PROTEINS; PHENOTYPE; RECEPTOR, INSULIN; SEQUENCE ALIGNMENT; SOMATOMEDINS; TRANSCRIPTION FACTORS;

CAENORHABDITIS ELEGANS;

EID: 0030657540     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.278.5341.1319     Document Type: Article

References (40)

1. S. M. Jazwinski, Science 273, 54 (1996); T. Smeal and L. Guarante, Curr. Opin. Genet. Dev. 7, 281 (1997); C. Kenyon, Cell 84, 501 (1996).
2. S. M. Jazwinski, Science 273, 54 (1996); T. Smeal and L. Guarante, Curr. Opin. Genet. Dev. 7, 281 (1997); C. Kenyon, Cell 84, 501 (1996).
3. S. M. Jazwinski, Science 273, 54 (1996); T. Smeal and L. Guarante, Curr. Opin. Genet. Dev. 7, 281 (1997); C. Kenyon, Cell 84, 501 (1996).
4. C. Kenyon, in C. elegans II, D. R. Riddle, T. Blumenthal, B. Meyer, J. Priess, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1997), pp. 791-814.
5. K. D. Kimura, H. A. Tissenbaum, Y. Liu, G. Ruvkun, Science 277, 942 (1997).
6. C. Kenyon, J. Chang, E. Gensch, A. Rudner, R. Tabtiang, Nature 366, 461 (1993).
7. P. L. Larsen, P. S. Albert, D. L. Riddle, Genetics 139, 1567 (1995).
8. J. R. Vanfleteren and A. DeVreese, FASEB J. 9, 1355 (1995); J. Exp. Zool. 274, 93 (1996).
9. J. R. Vanfleteren and A. DeVreese, FASEB J. 9, 1355 (1995); J. Exp. Zool. 274, 93 (1996).
10. D. L. Riddle, M. M. Swanson, P. S. Albert, Nature 290, 668 (1981).
11. S. Gottlieb and G. Ruvkun, Genetics 137, 107 (1994).
12. D. Riddle and P. S. Albert, in C. elegans II, D. R. Riddle, T. Blumenthal, B. Meyer, J. Priess, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1997), pp. 739-768.
13. J. J. Vowels and J. H. Thomas, Genetics 130, 105 (1992).
14. The process of dauer formation is facilitated by high temperature; therefore, many daf-2 mutations induce dauer formation at high but not low temperature. At low temperature (or when shifted to high temperature as young adults, past the dauer decision point), these daf-2 mutants become long-lived adults (4).
15. Because dauers are long-lived, one explanation for these two roles is that weak daf-2 mutations allow adults to express only one feature of the dauer, namely its slow rate of aging.
16. M. D. Yandell, L. G. Edgar, W. B. Wood, Proc. Natl. Acad. Sci. U.S.A. 91, 1381 (1994).
17. 2 progeny of mutagenized animals, we would have missed mutants that were maternally rescued.
18. We first attempted to clone daf-16 by positional mapping but found that the gene was located in a gap in the physical map between cosmids AE7 and ZK39. To isolate daf-16::Tc1 insertion mutants, we screened daf-2(sa189); mut-6 animals for spontaneous mutants that did not become dauere when cultured at 20°C. One mutant, mu147, also suppressed dauer formation at 25°C. This mutation failed to complement daf-16(m26) and was closely linked to unc-29, which maps near daf-16. mu147 was subsequently crossed to either unc-29(e1072); daf-2(e1370); him-5(e1490) or daf-2(e1370); him-5(e1490) mutants, and homozygous Daf-16(-) and Daf-16(+) recombinants were obtained. Genomic DNA was prepared from these recombinants and analyzed by Southern blot hybridization with the 1.6-kb Tc1 sequence as probe. A 6.1-kb Tc1-hybridizing fragment was detected in the Xba I-digested genomic DNA, which was present in 20 of 20 daf-16(-) recombinants but absent in 15 of 15daf-16(+) recombinants and also absent in the wild-type strain (N2). DNA from the corresponding region was then extracted from agarose gels and circularized by self-ligation. An inverse PCR strategy was used to identify a Tc1-containing fragment with the expected size of 5.1 kb. The Tc1-specific primers used for inverse PCR were 5′-CCTTGTTCGAAGCCAGCTACAATGGC-3′ and 5′-TGATCGACTCGATGCCACGTCGTTGT-3′. The 5.1-kb PCR product was cloned into the pGEM-T vector (Promega, Madison, WI), and the 0.6-kb flanking Tc1 sequence was removed by digestion with Eco RV. The remaining sequence was then used as a probe in subsequent experiments.
19. R. H. A. Plasterk and H. G. A. M. van Luenen, in C. elegans II, D. R. Riddle, T. Blumenthal, B. Meyer, J. Priess, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1997), pp. 97-116.
20. J. Sulston et al., Nature 356, 37 (1992); R. Wilson et al., ibid. 368, 32 (1994).
21. J. Sulston et al., Nature 356, 37 (1992); R. Wilson et al., ibid. 368, 32 (1994).
22. I, to obtain the 3′ end by rapid amplification of cDNA ends (RACE), as well as with several internal primers (positioned as shown in Fig. 2B). In addition, blast searches with sequences contained on R13H8 identified three cDNA clones (yk13f11, yk31f10, and yk32f8) in a C. elegans EST database. Complete sequences of clones yk13f11 and yk31f10 were then obtained, and both contained the longer form of the transcripts, whereas the majority of the RT-PCR products (with mixed-stage RNA preparations) contained the shorter form (see Fig. 2). In addition, the longer spliced form was also detected by RT-PCR.
23. E. Kaufmann and W. Knochel, Mech. Dev. 57, 3 (1996).
24. K. Lin, J. Dorman, A. Rodan, C. Kenyon, data not shown.
25. X. Chen et al., Nature 389, 85 (1997).
26. P. Flakoll, M. G. Carlson, A. Cherrington, in Diabetes Mellitus, D. LeRoith, S. I. Taylor, J. M. Olefsky, Eds. (Lippincott-Raven, Philadelphia, PA, 1996), pp. 121-131.
27. R. M. O'Brien and D. K. Granner, in ibid., pp. 234-241.
28. R. M. O'Brien et al., Mol. Cell. Biol. 15, 1747 (1995).
29. D. B. Friedman and T. E. Johnson, Genetics 118, 75 (1988).
30. J. Z. Morris, H. A. Tissenbaum, G. Ruvkun, Nature 382, 536 (1996).
31. J. B. Dorman, B. Albinder, T. Shroyer, C. Kenyon, Genetics 141, 1399 (1995).
32. S. Murakami and T. E. Johnson, ibid. 143, 1207 (1996).
33. Neither gain of function (n1046) nor dominant negative (sy100) mutations in the C. elegans Ras homolog let-60 affected C. elegans life-span (because these mutants cannot lay eggs, their gonads were ablated to prevent premature death from internal hatching). In addition, let-60(n1046gf) did not suppress the dauer-constitutive phenotype of daf-2(e1370) (J. Apfeld and C. Kenyon, unpublished data).
34. C. E. Finch, Longevity, Senescence, and the Genome (Univ. of Chicago Press, Chicago, IL, 1990).
35. B. D. Williams et al., Genetics 131, 609 (1992).
36. M. Krause and D. Hirsh, Cell 49, 753 (1987).
37. M. A. Frohman, Methods Enzymol. 28, 341 (1993).
38. K. L. Clark, E. D. Halay, E. Lai, S. K. Burley, Nature 364, 412 (1993).
39. S. Ogg et al., ibid. 389, 994 (1997).
40. We thank N. Ahmada for technical assistance with positional mapping (16); B. Albinder, M. Macrae, J. Reiter, T. Wang, D. Eisenstadt, I. Reichardt, and J. Blumstein for helping to isolate and characterize trimethylpsoraten-and Tc1-induced daf-16 mutants; J. Apfeld in our laboratory for investigating the role of Ras in the daf-2 signaling pathways (30); members of the Kenyon lab for discussions and comments on the manuscript; and Y. Kohara for sending us EST clones of daf-16. Supported by NIH grant AG11816. C.K. is the Herbert Boyer Professor of Biochemistry and Biophysics.