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. 1987 Dec;84(24):9020–9024. doi: 10.1073/pnas.84.24.9020

Changes in translational yield regulate tissue-specific expression of beta-glucuronidase.

L T Bracey 1, K Paigen 1
PMCID: PMC299683  PMID: 3480527

Abstract

The number of beta-glucuronidase (GUS; beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) molecules per cell varies as much as 12-fold among mouse tissues. To identify the regulatory mechanisms responsible, estimates of the rates of GUS protein synthesis (ks) and degradation (kd) were obtained for six tissues in the B6.PAC-Gusn mouse strain, which carries the N haplotype of the GUS gene. Differences in enzyme levels among tissues were predominantly due to differences in rates of enzyme synthesis; only brain differed significantly in the rate of protein degradation. Typically, tissues contain about 2 molecules of GUS mRNA per cell. Differences in GUS mRNA levels were found among tissues, but these were not sufficient to account for observed differences in ks. This suggests that tissues differ in translational yield, which is defined as the product of the efficiency with which the GUS message is translated and the fraction of newly made polypeptides that are successfully matured into GUS tetramers. Experimental estimates of translational yield confirmed that this is indeed a source of tissue differences in GUS gene regulation. This finding also proved to be true of the B haplotype of the GUS gene. The differential regulation of special-function genes is, in general, effected transcriptionally. In contrast, the differential regulation of several "housekeeping" genes has been reported to arise from changes in mRNA maturation and/or stability. It is now apparent that translational yield, which is an aspect of protein synthesis, can also serve as a differential regulatory mechanism.

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Selected References

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

  1. Alton T. H., Lodish H. F. Translational control of protein synthesis during the early stages of differentiation of the slime mold Dictyostelium discoideum. Cell. 1977 Sep;12(1):301–310. doi: 10.1016/0092-8674(77)90208-2. [DOI] [PubMed] [Google Scholar]
  2. Berry J. O., Nikolau B. J., Carr J. P., Klessig D. F. Translational regulation of light-induced ribulose 1,5-bisphosphate carboxylase gene expression in amaranth. Mol Cell Biol. 1986 Jul;6(7):2347–2353. doi: 10.1128/mcb.6.7.2347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop J. O., Morton J. G., Rosbash M., Richardson M. Three abundance classes in HeLa cell messenger RNA. Nature. 1974 Jul 19;250(463):199–204. doi: 10.1038/250199a0. [DOI] [PubMed] [Google Scholar]
  4. Catterall J. F., Leary S. L. Detection of early changes in androgen-induced mouse renal beta-glucuronidase messenger ribonucleic acid using cloned complementary deoxyribonucleic acid. Biochemistry. 1983 Dec 20;22(26):6049–6053. doi: 10.1021/bi00295a001. [DOI] [PubMed] [Google Scholar]
  5. Cleveland D. W., Havercroft J. C. Is apparent autoregulatory control of tubulin synthesis nontranscriptionally regulated? J Cell Biol. 1983 Sep;97(3):919–924. doi: 10.1083/jcb.97.3.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  7. Galau G. A., Klein W. H., Britten R. J., Davidson E. H. Significance of rare m RNA sequences in liver. Arch Biochem Biophys. 1977 Mar;179(2):584–599. doi: 10.1016/0003-9861(77)90147-3. [DOI] [PubMed] [Google Scholar]
  8. Galau G. A., Klein W. H., Davis M. M., Wold B. J., Britten R. J., Davidson E. H. Structural gene sets active in embryos and adult tissues of the sea urchin. Cell. 1976 Apr;7(4):487–505. doi: 10.1016/0092-8674(76)90200-2. [DOI] [PubMed] [Google Scholar]
  9. Gan J. C., Jeffay H. Origins and metabolism of the intracellular amino acid pools in rat liver and muscle. Biochim Biophys Acta. 1967 Nov 28;148(2):448–459. doi: 10.1016/0304-4165(67)90141-9. [DOI] [PubMed] [Google Scholar]
  10. Groudine M., Casimir C. Post-transcriptional regulation of the chicken thymidine kinase gene. Nucleic Acids Res. 1984 Feb 10;12(3):1427–1446. doi: 10.1093/nar/12.3.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hastie N. D., Bishop J. O. The expression of three abundance classes of messenger RNA in mouse tissues. Cell. 1976 Dec;9(4 Pt 2):761–774. doi: 10.1016/0092-8674(76)90139-2. [DOI] [PubMed] [Google Scholar]
  12. Hinnebusch A. G. Evidence for translational regulation of the activator of general amino acid control in yeast. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442–6446. doi: 10.1073/pnas.81.20.6442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Itoh N., Okamoto H. Translational control of proinsulin synthesis by glucose. Nature. 1980 Jan 3;283(5742):100–102. doi: 10.1038/283100a0. [DOI] [PubMed] [Google Scholar]
  14. Kaufman R. J., Sharp P. A. Growth-dependent expression of dihydrofolate reductase mRNA from modular cDNA genes. Mol Cell Biol. 1983 Sep;3(9):1598–1608. doi: 10.1128/mcb.3.9.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LOFTFIELD R. B., HARRIS A. Participation of free amino acids in protein synthesis. J Biol Chem. 1956 Mar;219(1):151–159. [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  18. Labarca C., Paigen K. MRNA-directed synthesis of catalytically active mouse beta-glucuronidase in Xenopus oocytes. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4462–4465. doi: 10.1073/pnas.74.10.4462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lindquist S. Regulation of protein synthesis during heat shock. Nature. 1981 Sep 24;293(5830):311–314. doi: 10.1038/293311a0. [DOI] [PubMed] [Google Scholar]
  20. Lusis A. J., Paigen K. The large scale isolation of mouse beta-glucuronidase and comparison of allozymes. J Biol Chem. 1978 Oct 25;253(20):7336–7345. [PubMed] [Google Scholar]
  21. Lüscher B., Stauber C., Schindler R., Schümperli D. Faithful cell-cycle regulation of a recombinant mouse histone H4 gene is controlled by sequences in the 3'-terminal part of the gene. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4389–4393. doi: 10.1073/pnas.82.13.4389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meyer D. I., Krause E., Dobberstein B. Secretory protein translocation across membranes-the role of the "docking protein'. Nature. 1982 Jun 24;297(5868):647–650. doi: 10.1038/297647a0. [DOI] [PubMed] [Google Scholar]
  23. Nadal-Ginard B. Regulation of lactate dehydrogenase levels in the mouse. J Biol Chem. 1978 Jan 10;253(1):170–177. [PubMed] [Google Scholar]
  24. Nevins J. R. The pathway of eukaryotic mRNA formation. Annu Rev Biochem. 1983;52:441–466. doi: 10.1146/annurev.bi.52.070183.002301. [DOI] [PubMed] [Google Scholar]
  25. Oshima A., Kyle J. W., Miller R. D., Hoffmann J. W., Powell P. P., Grubb J. H., Sly W. S., Tropak M., Guise K. S., Gravel R. A. Cloning, sequencing, and expression of cDNA for human beta-glucuronidase. Proc Natl Acad Sci U S A. 1987 Feb;84(3):685–689. doi: 10.1073/pnas.84.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ouellette A. J., Ordahl C. P., Van Ness J., Malt R. A. Mouse kidney nonpolysomal messenger ribonucleic acid: metabolism, coding function, and translational activity. Biochemistry. 1982 Mar 16;21(6):1169–1177. doi: 10.1021/bi00535a010. [DOI] [PubMed] [Google Scholar]
  27. Owerbach D., Luis A. J. Phenobarbital induction of egasyn: availability of egasyn in vivo determines glucuronidase binding to membrane. Biochem Biophys Res Commun. 1976 Apr 5;69(3):628–634. doi: 10.1016/0006-291x(76)90922-0. [DOI] [PubMed] [Google Scholar]
  28. Palmer R., Gallagher P. M., Boyko W. L., Ganschow R. E. Genetic control of levels of murine kidney glucuronidase mRNA in response to androgen. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7596–7600. doi: 10.1073/pnas.80.24.7596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pfister K., Chapman V., Watson G., Paigen K. Genetic variation for enzyme structure and systemic regulation in two new haplotypes of the beta-glucuronidase gene of Mus musculus castaneus. J Biol Chem. 1985 Sep 25;260(21):11588–11594. [PubMed] [Google Scholar]
  30. Pfister K., Watson G., Chapman V., Paigen K. Kinetics of beta-glucuronidase induction by androgen. Genetic variation in the first order rate constant. J Biol Chem. 1984 May 10;259(9):5816–5820. [PubMed] [Google Scholar]
  31. Piechaczyk M., Blanchard J. M., Marty L., Dani C., Panabieres F., El Sabouty S., Fort P., Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. doi: 10.1093/nar/12.18.6951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rosenfeld M. G., Kreibich G., Popov D., Kato K., Sabatini D. D. Biosynthesis of lysosomal hydrolases: their synthesis in bound polysomes and the role of co- and post-translational processing in determining their subcellular distribution. J Cell Biol. 1982 Apr;93(1):135–143. doi: 10.1083/jcb.93.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ryffel G. U., McCarthy B. J. Complexity of cytoplasmic RNA in different mouse tissues measured by hybridization of polyadenylated RNA to complementary DNA. Biochemistry. 1975 Apr 8;14(7):1379–1385. doi: 10.1021/bi00678a006. [DOI] [PubMed] [Google Scholar]
  34. Schimke R. T., Doyle D. Control of enzyme levels in animal tissues. Annu Rev Biochem. 1970;39:929–976. doi: 10.1146/annurev.bi.39.070170.004433. [DOI] [PubMed] [Google Scholar]
  35. Schimke R. T., Sweeney E. W., Berlin C. M. An analysis of the kinetics of rat liver tryptophan pyrrolase induction: the significance of both enzyme synthesis and degradation. Biochem Biophys Res Commun. 1964 Mar 26;15(3):214–219. doi: 10.1016/0006-291x(64)90148-2. [DOI] [PubMed] [Google Scholar]
  36. Smith K., Ganschow R. E. Turnover of murine beta-glucuronidase. Comparison among liver, kidney, and spleen and between lysosomes and microsomes. J Biol Chem. 1978 Aug 10;253(15):5437–5442. [PubMed] [Google Scholar]
  37. Suzuki Y., Kikuchi H., Kato C., Horiuchi Y., Tomita K. Effect of alkyl phosphates on beta-glucuronidase in rats: release of beta-glucuronidase from liver microsomes into serum. Biochem Pharmacol. 1977 May 1;26(9):881–885. doi: 10.1016/0006-2952(77)90404-x. [DOI] [PubMed] [Google Scholar]
  38. Swank R. T., Moore K., Chapman V. M. Abnormal subcellular distribution of beta-glucuronidase in mice with a genetic alteration in enzyme structure. Biochem Genet. 1987 Feb;25(1-2):161–174. doi: 10.1007/BF00498959. [DOI] [PubMed] [Google Scholar]
  39. Thireos G., Penn M. D., Greer H. 5' untranslated sequences are required for the translational control of a yeast regulatory gene. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5096–5100. doi: 10.1073/pnas.81.16.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Walter P., Blobel G. Translocation of proteins across the endoplasmic reticulum III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J Cell Biol. 1981 Nov;91(2 Pt 1):557–561. doi: 10.1083/jcb.91.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Watson G., Felder M., Rabinow L., Moore K., Labarca C., Tietze C., Vander Molen G., Bracey L., Brabant M., Cai J. D. Properties of rat and mouse beta-glucuronidase mRNA and cDNA, including evidence for sequence polymorphism and genetic regulation of mRNA levels. Gene. 1985;36(1-2):15–25. doi: 10.1016/0378-1119(85)90065-4. [DOI] [PubMed] [Google Scholar]
  42. Watson G., Paigen K. Genetic variations in kinetic constants that describe beta-glucuronidase mRNA induction in androgen-treated mice. Mol Cell Biol. 1987 Mar;7(3):1085–1090. doi: 10.1128/mcb.7.3.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Watson G., Paigen K. Segregation of genetic determinants for murine glucuronidase synthesis and loss in CXB recombinant-inbred strains. Biochem Genet. 1978 Oct;16(9-10):897–903. doi: 10.1007/BF00483741. [DOI] [PubMed] [Google Scholar]
  44. Wickner W. T., Lodish H. F. Multiple mechanisms of protein insertion into and across membranes. Science. 1985 Oct 25;230(4724):400–407. doi: 10.1126/science.4048938. [DOI] [PubMed] [Google Scholar]
  45. Yamamoto K. R., Alberts B. M. Steroid receptors: elements for modulation of eukaryotic transcription. Annu Rev Biochem. 1976;45:721–746. doi: 10.1146/annurev.bi.45.070176.003445. [DOI] [PubMed] [Google Scholar]

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