Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Most of the coding region of rat ACTHβ–LPH precursor gene lacks intervening sequences

Abstract

The peptide hormones ACTH, β-endorphin, α- and β-melanotropin(MSH) and possibly γ-MSH are synthesized in the pituitary gland by the processing of a 32,000-molecuIar weight (MW) polypeptide called proopiomelanocortin (POMC)1–5. The existence of a further precursor (pre form) to POMC containing an additional N-terminal ‘leader’ peptide has been suggested by analysis of the in vitro translation products of poly(A)-containing RNA from AtT-20 cells, a mouse ACTH-producing cell line of pituitary origin6. Nakanishi et al.7 cloned and sequenced a cDNA copy of the bovine prePOMC mRNA. This sequence confirmed the known structure of the carboxyl half of POMC and revealed the presence of a new MSH-like moiety, γ-MSH, within the 16,000-MW amino half of the precursor (16K fragment). Recent experiments have suggested that this peptide may act in synergy with ACTH to increase corticosterone and aldosterone production in vivo and in vitro8,9. We have now isolated from a rat genomic DNA library10 a segment of a DNA encoding most of POMC, using as probe a mouse 144-base pair cloned cDNA fragment encoding β-MSH and β-endorphin11. The cloned rat gene is one of two (or more) closely related POMC genes. The DNA sequence obtained shows that the cloned POMC gene is not interrupted by any intervening sequence (IVS) between the codon for amino acid 19 and the presumptive poly(A) addition site. This region of POMC encodes all the biologically active peptides mentioned above. The DNA sequence encoding the putative γ-MSH and the coding sequence that precedes it are highly conserved between rat and cow. This may indicate an as yet unrecognized biological function(s) for the NH2-terminal portion of the 16K fragment.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Roberts, J. L. & Herbert, E. Proc. natn. Acad. Sci. U.S.A. 74, 4826–4830 (1977).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Mains, R. E., Eipper, B. A. & Ling, N. Proc. natn. Acad. Sci. U.S.A. 74, 3014–3018 (1977).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Eipper, B. A. & Mains, R. E. J. supramolec. Struct. 8, 247–262 (1978).

    CAS  Article  Google Scholar 

  4. 4

    Roberts, J. L., Phillips, M., Rosen, P. A. & Herbert, E. Biochemistry 17, 3609–3618 (1978).

    CAS  Article  Google Scholar 

  5. 5

    Crine, P. et al. Proc. natn. Acad. Sci. U.S.A. 75, 4719–4723 (1978).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Gossard, F., Seidah, N. G., Crine, P., Routhier, R. & Chretien, M. Biochem. biophys. Res. Commun. 92, 1042–1051 (1980).

    CAS  Article  Google Scholar 

  7. 7

    Nakanishi, S. et al. Nature 278, 423–427 (1979).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Pedersen, R. C. & Brownie, A. C. Proc. natn. Acad. Sci. U.S.A. 77, 2239–2245 (1980).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Pedersen, R. C., Brownie, A. C. & Ling, N. Science 208, 1044–1045 (1980).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Maniatis, T. et al. Cell 15, 687–701 (1978).

    CAS  Article  Google Scholar 

  11. 11

    Roberts, J. L. et al. Proc. natn. Acad. Sci. U.S.A. 76, 2153–2157 (1979).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Grunstein, M. & Hogness, D. S. Proc. natn. Acad. Sci. U.S.A. 72, 3961–3965 (1975).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    CAS  Article  Google Scholar 

  14. 14

    Jeffreys, A. J. & Flavell, R. A. Cell 12, 429–439 (1977).

    CAS  Article  Google Scholar 

  15. 15

    Rigby, P. W. J., Dieckmann, M., Rhodes, C. & Berg, P. J. molec. Biol. 113, 237–251 (1977).

    CAS  Article  Google Scholar 

  16. 16

    Thompson, E. B., Tomkins, G. M. & Curran, J. F. Proc. natn. Acad. Sci. U.S.A. 56, 296–303 (1966).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Cordell, B. et al. Cell 18, 533–543 (1979).

    CAS  Article  Google Scholar 

  18. 18

    Lomedico, P. et al. Cell 18, 545–558 (1979).

    CAS  Article  Google Scholar 

  19. 19

    Seidah, N. G. et al. Biochem. biophys. Res. Commun. 95, 1417–1424 (1980).

    CAS  Article  Google Scholar 

  20. 20

    Seif, I., Khoury, G. & Dhar, R. Nucleic Acids Res. 6, 3387 (1979).

    CAS  Article  Google Scholar 

  21. 21

    Gianoulakis, C., Seidah, N. G., Routhier, R. & Chretien, M. Int. J. Peptide Protein Res. (in the press).

  22. 22

    Crine, P. et al. Biochemistry (in the press).

  23. 23

    Dayhoff, M. O. Atlas of Protein Sequence and Structure Vol. 5, D194–D197 (Natn. Biomed. Res. Fdn, Washington, DC, 1972).

    Google Scholar 

  24. 24

    Bloomfield, G. A., Scott, A. P., Lowry, P. J., Gilkes, J. J. H. & Rees, L. H. Nature 252, 492–495 (1974).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Mains, R. E. & Eipper, B. A. in Endorphins (eds Graff, L., Palkovits, M. & Ronai, A. Z.) 79–126 (Akademia Kiado, Budapest, 1978).

    Google Scholar 

  26. 26

    Proudfoot, N. J. & Brownlee, G. G. Nature 263, 211–214 (1976).

    ADS  CAS  Article  Google Scholar 

  27. 27

    Benoist, C., O'Hare, K., Breathnach, R. & Chambon, P. Nucleic Acids Res. 8, 127–142 (1980).

    CAS  Article  Google Scholar 

  28. 28

    Gilbert, W. Nature 271, 501 (1978).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Darnell, J. Science 202, 1257–1260 (1978).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Doolittle, W. Nature 272, 581–582 (1978).

    ADS  Article  Google Scholar 

  31. 31

    Eaton, W. A. Nature 284, 183–185 (1980).

    ADS  CAS  Article  Google Scholar 

  32. 32

    Craik, C. S., Buchman, S. R. & Beychok, S. Proc. natn. Acad. Sci. U.S.A. 77, 1384–1388 (1980).

    ADS  CAS  Article  Google Scholar 

  33. 33

    Chang, A. C. Y., Cochet, M. & Cohen, S. N. Proc. natn. Acad. Sci. U.S.A. 77, 4890–4894 (1980).

    ADS  CAS  Article  Google Scholar 

  34. 34

    Nakanishi, S. et. al. Nature 287, 752–755 (1980).

    ADS  CAS  Article  Google Scholar 

  35. 35

    Blattner, F. R. et al. Science 196, 161–169 (1977).

    ADS  CAS  Article  Google Scholar 

  36. 36

    Daniels, D. L., de Wet, J. R. & Blattner, F. F. J. Virol. 33, 390–400 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Barnes, W. M. Science 195, 393–394 (1977).

    ADS  CAS  Article  Google Scholar 

  38. 38

    Sutcliffe, J. G. Nucleic Acids Res. 5, 2721–2728 (1978).

    CAS  Article  Google Scholar 

  39. 39

    Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    ADS  CAS  Article  Google Scholar 

  40. 40

    Messing, J., Gronenborn, B., Muller-Hill, B. & Hofschneider, P. H. Proc. natn. Acad. Sci. U.S.A. 71, 3612–3616 (1977).

    Google Scholar 

  41. 41

    Gronenborn, B. & Messing, J. Nature 272, 375–377 (1978).

    ADS  CAS  Article  Google Scholar 

  42. 42

    Winter, G. & Fields, S. Nucleic Acids Res. 8, 1965–1974 (1980).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Drouin, J., Goodman, H. Most of the coding region of rat ACTHβ–LPH precursor gene lacks intervening sequences. Nature 288, 610–613 (1980). https://doi.org/10.1038/288610a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing