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. 1987 Oct;84(20):7261–7265. doi: 10.1073/pnas.84.20.7261

Characterization of proopiomelanocortin transcripts in human nonpituitary tissues.

T Lacaze-Masmonteil 1, Y de Keyzer 1, J P Luton 1, A Kahn 1, X Bertagna 1
PMCID: PMC299272  PMID: 3478693

Abstract

Proopiomelanocortin (POMC), the precursor to adrenocorticotropic hormone and other related peptides, was originally identified in the corticotropic cell. Recent evidence shows that POMC products are also normally present in a variety of nonpituitary tissues. To investigate this phenomenon in humans we looked for the presence and characteristics of POMC transcripts in various adult tissues. Blot hybridization analysis of normal adrenal, thymus, and testis RNAs revealed a small RNA species approximately 400 nucleotides shorter than the 1200-nucleotide pituitary species. Primer extension and S1 nuclease mapping studies showed that this small RNA lacked exon 1 and exon 2 of the gene, and it corresponded to a set of at least six molecules starting 41 to 162 nucleotides downstream from the 5' end of exon 3. These RNAs appear to result from heterogeneous transcription initiation sites presumably under the control of "GC box" promoter sequences located in the 3' end of intron 2. They cannot encode a complete POMC molecule, and the only truncated POMC molecules that could be translated would lack a signal peptide necessary for membrane translocation and precursor processing. The use of highly sensitive S1 nuclease mapping techniques with uniformly labeled single-stranded DNA probes allowed the detection of a small but definite amount of the "normal," 1200-nucleotide, mRNA species. It is suggested that it is this POMC mRNA that is responsible for the local production of all the POMC peptides.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bailey J. M., Davidson N. Methylmercury as a reversible denaturing agent for agarose gel electrophoresis. Anal Biochem. 1976 Jan;70(1):75–85. doi: 10.1016/s0003-2697(76)80049-8. [DOI] [PubMed] [Google Scholar]
  3. Bardin C. W., Shaha C., Mather J., Salomon Y., Margioris A. N., Liotta A. S., Gerendai I., Chen C. L., Krieger D. T. Identification and possible function of pro-opiomelanocortin-derived peptides in the testis. Ann N Y Acad Sci. 1984;438:346–364. doi: 10.1111/j.1749-6632.1984.tb38296.x. [DOI] [PubMed] [Google Scholar]
  4. Boileau G., Barbeau C., Jeannotte L., Chrétien M., Drouin J. Complete structure of the porcine pro-opiomelanocortin mRNA derived from the nucleotide sequence of cloned cDNA. Nucleic Acids Res. 1983 Nov 25;11(22):8063–8071. doi: 10.1093/nar/11.22.8063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burke J. F. High-sensitivity S1 mapping with single-stranded [32P]DNA probes synthesized from bacteriophage M13mp templates. Gene. 1984 Oct;30(1-3):63–68. doi: 10.1016/0378-1119(84)90105-7. [DOI] [PubMed] [Google Scholar]
  6. Chen C. L., Mather J. P., Morris P. L., Bardin C. W. Expression of pro-opiomelanocortin-like gene in the testis and epididymis. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5672–5675. doi: 10.1073/pnas.81.18.5672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen M. J., Shimada T., Moulton A. D., Cline A., Humphries R. K., Maizel J., Nienhuis A. W. The functional human dihydrofolate reductase gene. J Biol Chem. 1984 Mar 25;259(6):3933–3943. [PubMed] [Google Scholar]
  8. Civelli O., Birnberg N., Herbert E. Detection and quantitation of pro-opiomelanocortin mRNA in pituitary and brain tissues from different species. J Biol Chem. 1982 Jun 25;257(12):6783–6787. [PubMed] [Google Scholar]
  9. Drouin J., Goodman H. M. Most of the coding region of rat ACTH beta--LPH precursor gene lacks intervening sequences. Nature. 1980 Dec 11;288(5791):610–613. doi: 10.1038/288610a0. [DOI] [PubMed] [Google Scholar]
  10. Dynan W. S., Sazer S., Tjian R., Schimke R. T. Transcription factor Sp1 recognizes a DNA sequence in the mouse dihydrofolate reductase promoter. Nature. 1986 Jan 16;319(6050):246–248. doi: 10.1038/319246a0. [DOI] [PubMed] [Google Scholar]
  11. Eberwine J. H., Roberts J. L. Analysis of pro-opiomelancortin gene structure and function. DNA. 1983;2(1):1–8. doi: 10.1089/dna.1.1983.2.1. [DOI] [PubMed] [Google Scholar]
  12. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  13. Gizang-Ginsberg E., Wolgemuth D. J. Localization of mRNAs in mouse testes by in situ hybridization: distribution of alpha-tubulin and developmental stage specificity of pro-opiomelanocortin transcripts. Dev Biol. 1985 Oct;111(2):293–305. doi: 10.1016/0012-1606(85)90484-1. [DOI] [PubMed] [Google Scholar]
  14. Kahn A., Cottreau D., Daegelen D., Dreyfus J. C. Cell-free translation of messenger RNAs from adult and fetal human muscle. Characterization of neosynthesized glycogen phosphorylase, phosphofructokinase and glucose phosphate isomerase. Eur J Biochem. 1981 May;116(1):7–12. doi: 10.1111/j.1432-1033.1981.tb05293.x. [DOI] [PubMed] [Google Scholar]
  15. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mains R. E., Eipper B. A., Ling N. Common precursor to corticotropins and endorphins. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3014–3018. doi: 10.1073/pnas.74.7.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nakanishi S., Inoue A., Kita T., Nakamura M., Chang A. C., Cohen S. N., Numa S. Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. Nature. 1979 Mar 29;278(5703):423–427. doi: 10.1038/278423a0. [DOI] [PubMed] [Google Scholar]
  19. Nishikura K., ar-Rushdi A., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the normal and of the translocated human c-myc oncogenes in B cells. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4822–4826. doi: 10.1073/pnas.80.15.4822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pintar J. E., Schachter B. S., Herman A. B., Durgerian S., Krieger D. T. Characterization and localization of proopiomelanocortin messenger RNA in the adult rat testis. Science. 1984 Aug 10;225(4662):632–634. doi: 10.1126/science.6740329. [DOI] [PubMed] [Google Scholar]
  21. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
  22. Roberts J. L., Seeburg P. H., Shine J., Herbert E., Baxter J. D., Goodman H. M. Corticotropin and beta-endorphin: construction and analysis of recombinant DNA complementary to mRNA for the common precursor. Proc Natl Acad Sci U S A. 1979 May;76(5):2153–2157. doi: 10.1073/pnas.76.5.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shu-Dong T., Phillips D. M., Halmi N., Krieger D., Bardin C. W. Beta-endorphin is present in the male reproductive tract of five species. Biol Reprod. 1982 Oct;27(3):755–764. doi: 10.1095/biolreprod27.3.755. [DOI] [PubMed] [Google Scholar]
  24. Uhler M., Herbert E. Complete amino acid sequence of mouse pro-opiomelanocortin derived from the nucleotide sequence of pro-opiomelanocortin cDNA. J Biol Chem. 1983 Jan 10;258(1):257–261. [PubMed] [Google Scholar]
  25. Walter P., Gilmore R., Blobel G. Protein translocation across the endoplasmic reticulum. Cell. 1984 Aug;38(1):5–8. doi: 10.1016/0092-8674(84)90520-8. [DOI] [PubMed] [Google Scholar]
  26. Weintraub H., Larsen A., Groudine M. Alpha-Globin-gene switching during the development of chicken embryos: expression and chromosome structure. Cell. 1981 May;24(2):333–344. doi: 10.1016/0092-8674(81)90323-8. [DOI] [PubMed] [Google Scholar]
  27. de Keyzer Y., Bertagna X., Lenne F., Girard F., Luton J. P., Kahn A. Altered proopiomelanocortin gene expression in adrenocorticotropin-producing nonpituitary tumors. Comparative studies with corticotropic adenomas and normal pituitaries. J Clin Invest. 1985 Nov;76(5):1892–1898. doi: 10.1172/JCI112184. [DOI] [PMC free article] [PubMed] [Google Scholar]

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