Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Apr;15(4):2080–2089. doi: 10.1128/mcb.15.4.2080

Structure and expression of the guinea pig preproenkephalin gene: site-specific cleavage in the 3' untranslated region yields truncated mRNA transcripts in specific brain regions.

K S LaForge 1, E M Unterwald 1, M J Kreek 1
PMCID: PMC230435  PMID: 7891703

Abstract

We isolated the guinea pig preproenkephalin gene from a genomic library by hybridization to a rat cDNA probe. The entire nucleotide sequence of the gene was determined. Genomic Southern blot hybridization demonstrated that the gene exists in a single copy within the genome. On the basis of RNase protection transcript mapping and homology comparisons with known preproenkephalin sequences from other species and assuming a poly(A) tail length of 100 residues, we predicted an mRNA transcript of approximately 1,400 nucleotides encoded by three exons. Northern (RNA) blot analysis of total RNA from several brain regions showed high levels of preproenkephalin mRNA in the caudate putamen, nucleus accumbens, and hypothalamus, with detectable levels in the amygdala, ventral tegmental area, and central gray and also in the pituitary. Unexpectedly, in several brain regions, the mRNA appeared not only in the 1,400-nucleotide length but also in a shorter length of approximately 1,130 bases. Significant amounts of the shorter mRNA were found in the caudate putamen, nucleus accumbens, and amygdala. The longer, but not the shorter, transcripts from the caudate putamen were found to be polyadenylated, but the difference in size was not due solely to the presence of poly(A) tails. Northern gel analysis of total RNA from the caudate putamen with probes from each exon, together with RNase protection mapping of the 3' end of the mRNA demonstrated that the 1,400-base preproenkephalin mRNA transcripts are cleaved in a site-specific manner in some brain regions, yielding a 1,130-base transcript and a 165-base polyadenylated fragment derived from the terminal end of the 3' untranslated region of the mRNA. This cleavage may serve as a preliminary step in RNA degradation and provide a mechanism for control of preproenkephalin mRNA abundance through selective degradation.

Full Text

The Full Text of this article is available as a PDF (364.5 KB).

Selected References

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

  1. Aceto M. D., Dewey W. L., Chang J. K., Lee N. M. Dynorphin-(1-13): effects in nontolerant and morphine-dependent rhesus monkeys. Eur J Pharmacol. 1982 Sep 10;83(1-2):139–142. doi: 10.1016/0014-2999(82)90299-0. [DOI] [PubMed] [Google Scholar]
  2. Adesnik M., Darnell J. E. Biogenesis and characterization of histone messenger RNA in HeLa cells. J Mol Biol. 1972 Jun 28;67(3):397–406. doi: 10.1016/0022-2836(72)90458-5. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  5. Binder R., Hwang S. P., Ratnasabapathy R., Williams D. L. Degradation of apolipoprotein II mRNA occurs via endonucleolytic cleavage at 5'-AAU-3'/5'-UAA-3' elements in single-stranded loop domains of the 3'-noncoding region. J Biol Chem. 1989 Oct 5;264(28):16910–16918. [PubMed] [Google Scholar]
  6. Branch A. D., Unterwald E. M., Lee S. E., Kreek M. J. Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization assay. Brain Res Mol Brain Res. 1992 Jul;14(3):231–238. doi: 10.1016/0169-328x(92)90178-e. [DOI] [PubMed] [Google Scholar]
  7. Brilliant M. H., Sueoka N., Chikaraishi D. M. Cloning of DNA corresponding to rare transcripts of rat brain: evidence of transcriptional and post-transcriptional control and of the existence of nonpolyadenylated transcripts. Mol Cell Biol. 1984 Oct;4(10):2187–2197. doi: 10.1128/mcb.4.10.2187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brown B. D., Harland R. M. Endonucleolytic cleavage of a maternal homeo box mRNA in Xenopus oocytes. Genes Dev. 1990 Nov;4(11):1925–1935. doi: 10.1101/gad.4.11.1925. [DOI] [PubMed] [Google Scholar]
  9. Brown B. D., Zipkin I. D., Harland R. M. Sequence-specific endonucleolytic cleavage and protection of mRNA in Xenopus and Drosophila. Genes Dev. 1993 Aug;7(8):1620–1631. doi: 10.1101/gad.7.8.1620. [DOI] [PubMed] [Google Scholar]
  10. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chao H. M., McEwen B. S. Glucocorticoid regulation of preproenkephalin messenger ribonucleic acid in the rat striatum. Endocrinology. 1990 Jun;126(6):3124–3130. doi: 10.1210/endo-126-6-3124. [DOI] [PubMed] [Google Scholar]
  12. Chaudhari N., Hahn W. E. Genetic expression in the developing brain. Science. 1983 May 27;220(4600):924–928. doi: 10.1126/science.6189184. [DOI] [PubMed] [Google Scholar]
  13. Chikaraishi D. M. Complexity of cytoplasmic polyadenylated and nonpolyadenylated rat brain ribonucleic acids. Biochemistry. 1979 Jul 24;18(15):3249–3256. doi: 10.1021/bi00582a009. [DOI] [PubMed] [Google Scholar]
  14. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  15. Comb M., Birnberg N. C., Seasholtz A., Herbert E., Goodman H. M. A cyclic AMP- and phorbol ester-inducible DNA element. 1986 Sep 25-Oct 1Nature. 323(6086):353–356. doi: 10.1038/323353a0. [DOI] [PubMed] [Google Scholar]
  16. Comb M., Mermod N., Hyman S. E., Pearlberg J., Ross M. E., Goodman H. M. Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription. EMBO J. 1988 Dec 1;7(12):3793–3805. doi: 10.1002/j.1460-2075.1988.tb03264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Comb M., Seeburg P. H., Adelman J., Eiden L., Herbert E. Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA. Nature. 1982 Feb 25;295(5851):663–666. doi: 10.1038/295663a0. [DOI] [PubMed] [Google Scholar]
  18. Culpepper-Morgan J., Kreek M. J., Holt P. R., LaRoche D., Zhang J., O'Bryan L. Orally administered kappa as well as mu opiate agonists delay gastrointestinal transit time in the guinea pig. Life Sci. 1988;42(21):2073–2077. doi: 10.1016/0024-3205(88)90120-8. [DOI] [PubMed] [Google Scholar]
  19. Erickson J. M., Rushford C. L., Dorney D. J., Wilson G. N., Schmickel R. D. Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments. Gene. 1981 Dec;16(1-3):1–9. doi: 10.1016/0378-1119(81)90055-x. [DOI] [PubMed] [Google Scholar]
  20. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  21. Franklin R. M. Purification and properties of the replicative intermediate of the RNA bacteriophage R17. Proc Natl Acad Sci U S A. 1966 Jun;55(6):1504–1511. doi: 10.1073/pnas.55.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Franklin S. O., Yoburn B. C., Zhu Y. S., Branch A. D., Robertson H. D., Inturrisi C. E. Preproenkephalin mRNA and enkephalin in normal and denervated adrenals in the Syrian hamster: comparison with central nervous system tissues. Brain Res Mol Brain Res. 1991 Jun;10(3):241–250. doi: 10.1016/0169-328x(91)90067-8. [DOI] [PubMed] [Google Scholar]
  23. Fung B. P., Brilliant M. H., Chikaraishi D. M. Brain-specific polyA- transcripts are detected in polyA+ RNA: do complex polyA- brain RNAs really exist? J Neurosci. 1991 Mar;11(3):701–708. doi: 10.1523/JNEUROSCI.11-03-00701.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Glaser T., Hübner K., Hamprecht B. Glucocorticoids elevate the level of enkephalin-like peptides in neuroblastoma x glioma hybrid cells. FEBS Lett. 1981 Aug 17;131(1):63–67. doi: 10.1016/0014-5793(81)80888-5. [DOI] [PubMed] [Google Scholar]
  25. Gubler U., Seeburg P., Hoffman B. J., Gage L. P., Udenfriend S. Molecular cloning establishes proenkephalin as precursor of enkephalin-containing peptides. Nature. 1982 Jan 21;295(5846):206–208. doi: 10.1038/295206a0. [DOI] [PubMed] [Google Scholar]
  26. Hahn W. E., Chaudhari N., Beck L., Wilber K., Peffley D. Genetic expression and postnatal development of the brain: some characteristics of nonpolyadenylated mRNAs. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):465–475. doi: 10.1101/sqb.1983.048.01.051. [DOI] [PubMed] [Google Scholar]
  27. Harris D. A., Sherbany A. A. Cloning of non-polyadenylated RNAs from rat brain. Brain Res Mol Brain Res. 1991 Apr;10(1):83–90. doi: 10.1016/0169-328x(91)90059-7. [DOI] [PubMed] [Google Scholar]
  28. Höllt V., Sanchez-Blazquez P., Garzon J. Multiple opioid ligands and receptors in the control of nociception. Philos Trans R Soc Lond B Biol Sci. 1985 Feb 19;308(1136):299–312. doi: 10.1098/rstb.1985.0030. [DOI] [PubMed] [Google Scholar]
  29. Jones T. R., Cole M. D. Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. Mol Cell Biol. 1987 Dec;7(12):4513–4521. doi: 10.1128/mcb.7.12.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kaufmann Y., Milcarek C., Berissi H., Penman S. HeLa cell poly(A)- mRNA codes for a subset of poly(A)+ mRNA-directed proteins with an actin as a major product. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4801–4805. doi: 10.1073/pnas.74.11.4801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kilpatrick D. L., Howells R. D., Noe M., Bailey L. C., Udenfriend S. Expression of preproenkephalin-like mRNA and its peptide products in mammalian testis and ovary. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7467–7469. doi: 10.1073/pnas.82.21.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kilpatrick D. L., Rosenthal J. L. The proenkephalin gene is widely expressed within the male and female reproductive systems of the rat and hamster. Endocrinology. 1986 Jul;119(1):370–374. doi: 10.1210/endo-119-1-370. [DOI] [PubMed] [Google Scholar]
  33. Kilpatrick D. L., Zinn S. A., Fitzgerald M., Higuchi H., Sabol S. L., Meyerhardt J. Transcription of the rat and mouse proenkephalin genes is initiated at distinct sites in spermatogenic and somatic cells. Mol Cell Biol. 1990 Jul;10(7):3717–3726. doi: 10.1128/mcb.10.7.3717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
  35. La Gamma E. F., Adler J. E. Glucocorticoids regulate adrenal opiate peptides. Brain Res. 1987 Jul;388(2):125–130. doi: 10.1016/s0006-8993(87)80005-7. [DOI] [PubMed] [Google Scholar]
  36. Legon S., Glover D. M., Hughes J., Lowry P. J., Rigby P. W., Watson C. J. The structure and expression of the preproenkephalin gene. Nucleic Acids Res. 1982 Dec 20;10(24):7905–7918. doi: 10.1093/nar/10.24.7905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lightman S. L., Young W. S., 3rd Changes in hypothalamic preproenkephalin A mRNA following stress and opiate withdrawal. Nature. 1987 Aug 13;328(6131):643–645. doi: 10.1038/328643a0. [DOI] [PubMed] [Google Scholar]
  38. Martens G. J., Herbert E. Polymorphism and absence of Leu-enkephalin sequences in proenkephalin genes in Xenopus laevis. Nature. 1984 Jul 19;310(5974):251–254. doi: 10.1038/310251a0. [DOI] [PubMed] [Google Scholar]
  39. Meinsma D., Scheper W., Holthuizen P. E., Van den Brande J. L., Sussenbach J. S. Site-specific cleavage of IGF-II mRNAs requires sequence elements from two distinct regions of the IGF-II gene. Nucleic Acids Res. 1992 Oct 11;20(19):5003–5009. doi: 10.1093/nar/20.19.5003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Morrison M. R., Brodeur R., Pardue S., Baskin F., Hall C. L., Rosenberg R. N. Differences in the distribution of poly(A) size classes in individual messenger RNAs from neuroblastoma cells. J Biol Chem. 1979 Aug 25;254(16):7675–7683. [PubMed] [Google Scholar]
  42. Nadin-Davis S., Mezl V. A. Distribution of rat alpha-lactalbumin and casein mRNA between polyadenylated and nonpolyadenylated RNA. Can J Biochem Cell Biol. 1983 Jun;61(6):353–362. doi: 10.1139/o83-049. [DOI] [PubMed] [Google Scholar]
  43. Noda M., Furutani Y., Takahashi H., Toyosato M., Hirose T., Inayama S., Nakanishi S., Numa S. Cloning and sequence analysis of cDNA for bovine adrenal preproenkephalin. Nature. 1982 Jan 21;295(5846):202–206. doi: 10.1038/295202a0. [DOI] [PubMed] [Google Scholar]
  44. Noda M., Teranishi Y., Takahashi H., Toyosato M., Notake M., Nakanishi S., Numa S. Isolation and structural organization of the human preproenkephalin gene. Nature. 1982 Jun 3;297(5865):431–434. doi: 10.1038/297431a0. [DOI] [PubMed] [Google Scholar]
  45. Pandey N. B., Marzluff W. F. The stem-loop structure at the 3' end of histone mRNA is necessary and sufficient for regulation of histone mRNA stability. Mol Cell Biol. 1987 Dec;7(12):4557–4559. doi: 10.1128/mcb.7.12.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  47. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rattner A., Korner M., Rosen H., Baeuerle P. A., Citri Y. Nuclear factor kappa B activates proenkephalin transcription in T lymphocytes. Mol Cell Biol. 1991 Feb;11(2):1017–1022. doi: 10.1128/mcb.11.2.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Romano G. J., Mobbs C. V., Howells R. D., Pfaff D. W. Estrogen regulation of proenkephalin gene expression in the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone. Brain Res Mol Brain Res. 1989 Jan;5(1):51–58. doi: 10.1016/0169-328x(89)90017-x. [DOI] [PubMed] [Google Scholar]
  50. Rosen H., Douglass J., Herbert E. Isolation and characterization of the rat proenkephalin gene. J Biol Chem. 1984 Nov 25;259(22):14309–14313. [PubMed] [Google Scholar]
  51. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  53. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  54. Smith H. O., Birnstiel M. L. A simple method for DNA restriction site mapping. Nucleic Acids Res. 1976 Sep;3(9):2387–2398. doi: 10.1093/nar/3.9.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Snider B. J., Morrison-Bogorad M. Brain non-adenylated mRNAs. Brain Res Brain Res Rev. 1992 Sep-Dec;17(3):263–282. doi: 10.1016/0165-0173(92)90019-i. [DOI] [PubMed] [Google Scholar]
  56. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  57. Spiro C., Richards J. P., Chandrasekaran S., Brennan R. G., McMurray C. T. Secondary structure creates mismatched base pairs required for high-affinity binding of cAMP response element-binding protein to the human enkephalin enhancer. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4606–4610. doi: 10.1073/pnas.90.10.4606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Stoeckle M. Y., Hanafusa H. Processing of 9E3 mRNA and regulation of its stability in normal and Rous sarcoma virus-transformed cells. Mol Cell Biol. 1989 Nov;9(11):4738–4745. doi: 10.1128/mcb.9.11.4738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Stoeckle M. Y. Removal of a 3' non-coding sequence is an initial step in degradation of gro alpha mRNA and is regulated by interleukin-1. Nucleic Acids Res. 1992 Mar 11;20(5):1123–1127. doi: 10.1093/nar/20.5.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Takemori A. E., Loh H. H., Lee N. M. Suppression by dynorphin A-(1-13) of the expression of opiate withdrawal and tolerance in mice. Eur J Pharmacol. 1992 Oct 20;221(2-3):223–226. doi: 10.1016/0014-2999(92)90705-9. [DOI] [PubMed] [Google Scholar]
  61. Tavani A., Gambino M. C., Petrillo P. The opioid kappa-selective compound U-50,488H does not inhibit intestinal propulsion in rats. J Pharm Pharmacol. 1984 May;36(5):343–344. doi: 10.1111/j.2042-7158.1984.tb04391.x. [DOI] [PubMed] [Google Scholar]
  62. Theil E. C. Regulation of ferritin and transferrin receptor mRNAs. J Biol Chem. 1990 Mar 25;265(9):4771–4774. [PubMed] [Google Scholar]
  63. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Tulunay F. C., Jen M. F., Chang J. K., Loh H. H., Lee N. M. Possible regulatory role of dynorphin on morphine- and beta-endorphin-induced analgesia. J Pharmacol Exp Ther. 1981 Nov;219(2):296–298. [PubMed] [Google Scholar]
  65. Van Ness J., Maxwell I. H., Hahn W. E. Complex population of nonpolyadenylated messenger RNA in mouse brain. Cell. 1979 Dec;18(4):1341–1349. doi: 10.1016/0092-8674(79)90244-7. [DOI] [PubMed] [Google Scholar]
  66. Vournakis J. N., Efstratiadis A., Kafatos F. C. Electrophoretic patterns of deadenylylated chorion and globin mRNAs. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2959–2963. doi: 10.1073/pnas.72.8.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Vreken P., Raué H. A. The rate-limiting step in yeast PGK1 mRNA degradation is an endonucleolytic cleavage in the 3'-terminal part of the coding region. Mol Cell Biol. 1992 Jul;12(7):2986–2996. doi: 10.1128/mcb.12.7.2986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Weisinger G., DeCristofaro J. D., LaGamma E. F. Tissue- and treatment-specific usage of multiple preproenkephalin transcriptional start sites. J Biol Chem. 1992 Mar 5;267(7):4508–4512. [PubMed] [Google Scholar]
  69. Wilson T., Treisman R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences. Nature. 1988 Nov 24;336(6197):396–399. doi: 10.1038/336396a0. [DOI] [PubMed] [Google Scholar]
  70. Yanase T., Nawata H., Higuchi K., Kato K., Ibayashi H. Dexamethasone increases both catecholamines and methionine-enkephalin in cultured bovine adrenal chromaffin cells and human extramedullary pheochromocytoma cells. Life Sci. 1984 Oct 29;35(18):1869–1875. doi: 10.1016/0024-3205(84)90538-1. [DOI] [PubMed] [Google Scholar]
  71. Yoshikawa K., Maruyama K., Aizawa T., Yamamoto A. A new species of enkephalin precursor mRNA with a distinct 5'-untranslated region in haploid germ cells. FEBS Lett. 1989 Mar 27;246(1-2):193–196. doi: 10.1016/0014-5793(89)80281-9. [DOI] [PubMed] [Google Scholar]
  72. Yoshikawa K., Williams C., Sabol S. L. Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and distribution in the central nervous system. J Biol Chem. 1984 Nov 25;259(22):14301–14308. [PubMed] [Google Scholar]
  73. Zhu Y. S., Branch A. D., Robertson H. D., Inturrisi C. E. Cloning and characterization of hamster proenkephalin gene. DNA Cell Biol. 1994 Jan;13(1):25–35. doi: 10.1089/dna.1994.13.25. [DOI] [PubMed] [Google Scholar]
  74. Zukin R. S., Eghbali M., Olive D., Unterwald E. M., Tempel A. Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid receptors. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4061–4065. doi: 10.1073/pnas.85.11.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Zurawski G., Benedik M., Kamb B. J., Abrams J. S., Zurawski S. M., Lee F. D. Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis. Science. 1986 May 9;232(4751):772–775. doi: 10.1126/science.2938259. [DOI] [PubMed] [Google Scholar]
  76. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES