Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1975 Sep;150(3):335–344. doi: 10.1042/bj1500335

The effect of ethionine on ribonucleic acid synthesis in rat liver.

P F Swann
PMCID: PMC1165748  PMID: 1212195

Abstract

1. By 1h after administration of ethionine to the female rat the appearance of newly synthesized 18SrRNA in the cytoplasm is completely inhibited. This is not caused by inhibition of RNA synthesis, for the synthesis of the large ribosomal precursor RNA (45S) and of tRNA continues. Cleavage of 45S RNA to 32S RNA also occurs, but there was no evidence for the accumulation of mature or immature rRNA in the nucleus. 2. The effect of ethionine on the maturation of rRNA was not mimicked by an inhibitor of protein synthesis (cycloheximide) or an inhibitor of polyamine synthesis [methylglyoxal bis(guanylhydrazone)]. 3. Unlike the ethionine-induced inhibition of protein synthesis, this effect was not prevented by concurrent administration of inosine. A similar effect could be induced in HeLa cells by incubation for 1h in a medium lacking methionine. The ATP concentration in these cells was normal. From these two observations it was concluded that the effect of etionine on rRNA maturation is not caused by an ethionine-induced lack of ATP. It is suggested that ethionine, by lowering the hepatic concentration of S-adenosylmethionine, prevents methylation of the ribosomal precursor. The methylation is essential for the correct maturation of the molecule; without methylation complete degradation occurs.

Full text

PDF
344

Selected References

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

  1. BARTELS H., HOHORST H. J. [On the effect of ethionine on the metabolite status of the rat liver]. Biochim Biophys Acta. 1963 Apr 2;71:214–216. doi: 10.1016/0006-3002(63)91011-4. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blobel G., Potter V. R. Nuclei from rat liver: isolation method that combines purity with high yield. Science. 1966 Dec 30;154(3757):1662–1665. doi: 10.1126/science.154.3757.1662. [DOI] [PubMed] [Google Scholar]
  4. Brown D. D., Weber C. S. Gene linkage by RNA-DNA hybridization. I. Unique DNA sequences homologous to 4 s RNA, 5 s RNA and ribosomal RNA. J Mol Biol. 1968 Jun 28;34(3):661–680. doi: 10.1016/0022-2836(68)90188-5. [DOI] [PubMed] [Google Scholar]
  5. Corti A., Dave C., Williams-Ashman H. G., Mihich E., Schenone A. Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances. Biochem J. 1974 May;139(2):351–357. doi: 10.1042/bj1390351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dingman C. W., Peacock A. C. Analytical studies on nuclear ribonucleic acid using polyacrylamide gel electrophoresis. Biochemistry. 1968 Feb;7(2):659–668. doi: 10.1021/bi00842a022. [DOI] [PubMed] [Google Scholar]
  7. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  8. FARBER E. ETHIONINE CARCINOGENESIS. Adv Cancer Res. 1963;7:383–474. doi: 10.1016/s0065-230x(08)60986-0. [DOI] [PubMed] [Google Scholar]
  9. FARBER E., SHULL K. H., VILLA-TREVINO S., LOMBARDI B., THOMAS M. BIOCHEMICAL PATHOLOGY OF ACUTE HEPATIC ADENOSINETRIPHOSPHATE DEFICIENCY. Nature. 1964 Jul 4;203:34–40. doi: 10.1038/203034a0. [DOI] [PubMed] [Google Scholar]
  10. Farber E. Biochemical pathology. Annu Rev Pharmacol. 1971;11:71–96. doi: 10.1146/annurev.pa.11.040171.000443. [DOI] [PubMed] [Google Scholar]
  11. Farber E. Ethionine fatty liver. Adv Lipid Res. 1967;5:119–183. [PubMed] [Google Scholar]
  12. Farber E., Shull K. H., McConomy J. M., Castillo A. E. The effects of inosine and aminoimidazole carboxamide upon the ethionine fatty liver. Biochem Pharmacol. 1965 May;14(5):761–767. doi: 10.1016/0006-2952(65)90094-8. [DOI] [PubMed] [Google Scholar]
  13. Farber J. L., Farmar R. Differential effects of cycloheximide on protein and RNA synthesis as a function of dose. Biochem Biophys Res Commun. 1973 Apr 2;51(3):626–630. doi: 10.1016/0006-291x(73)91360-0. [DOI] [PubMed] [Google Scholar]
  14. Farber J. L., Shinozuka H., Serroni A., Farmar R. Reversal of the ethionine-induced inhibition of rat liver ribonucleic acid polymerases in vivo by adenine. Lab Invest. 1974 Nov;31(5):465–472. [PubMed] [Google Scholar]
  15. Fillingame R. H., Morris D. R. Polyamine accumulation during lymphocyte transformation and its relation to the synthesis, processing, and accumulation of ribonucleic acid. Biochemistry. 1973 Oct 23;12(22):4479–4487. doi: 10.1021/bi00746a028. [DOI] [PubMed] [Google Scholar]
  16. Goldblatt P. J., Witschi H., Friedman M. A., Sullivan R. J., Shull K. H. Some structural and functional consequences of hepatic adenosine triphosphate deficiency induced by intraperitoneal D-fructose administration. Lab Invest. 1970 Oct;23(4):378–385. [PubMed] [Google Scholar]
  17. Gumaa K. A., McLean P. The pentose phosphate pathway of glucose metabolism. Enzyme profiles and transient and steady-state content of intermediates of alternative pathways of glucose metabolism in Krebs ascites cells. Biochem J. 1969 Dec;115(5):1009–1029. doi: 10.1042/bj1151009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harik S. I., Hollenberg M. D., Snyder S. H. Alpha-hydrazino-ornithine blocks net synthesis of putrescine but not of RNA and DNA. Nature. 1974 May 17;249(454):250–251. doi: 10.1038/249250a0. [DOI] [PubMed] [Google Scholar]
  19. KELLER R., KELLER B. Réflexions sur le diagnostic et le traitement d'un kyste chyleux du mésentère. Rev Fr Gynecol Obstet. 1950 Jul-Aug;45(4):191–195. [PubMed] [Google Scholar]
  20. Kay J. E., Pegg A. E. Effect of inhibition of spermidine formation on protein and nucleic acid synthesis during lymphocyte activation. FEBS Lett. 1973 Feb 1;29(3):301–304. doi: 10.1016/0014-5793(73)80044-4. [DOI] [PubMed] [Google Scholar]
  21. Kisilevsky R., Shinozuka H., Benedetti E. L., Shull K. H., Farber E. Ribosomal alterations following ethionine intoxication. Lab Invest. 1973 Jan;28(1):8–15. [PubMed] [Google Scholar]
  22. Loening U. E. Molecular weights of ribosomal RNA in relation to evolution. J Mol Biol. 1968 Dec;38(3):355–365. doi: 10.1016/0022-2836(68)90391-4. [DOI] [PubMed] [Google Scholar]
  23. Monneron A., Burglen J., Bernhard W. Action of toyocamycin on nucleolar fine structure and function. J Ultrastruct Res. 1970 Aug;32(3):370–389. doi: 10.1016/s0022-5320(70)80016-8. [DOI] [PubMed] [Google Scholar]
  24. Munro H. N. The determination of nucleic acids. Methods Biochem Anal. 1966;14:113–176. doi: 10.1002/9780470110324.ch5. [DOI] [PubMed] [Google Scholar]
  25. Muramatsu M., Shimada N., Higashinakagawa T. Effect of cycloheximide on the nucleolar RNA synthesis in rat liver. J Mol Biol. 1970 Oct 14;53(1):91–106. doi: 10.1016/0022-2836(70)90047-1. [DOI] [PubMed] [Google Scholar]
  26. Oler A., Farber E., Shull K. H. Resistance of liver polysomes to ATP deficiency in the male rat. Biochim Biophys Acta. 1969 Sep 17;190(1):161–169. doi: 10.1016/0005-2787(69)90165-8. [DOI] [PubMed] [Google Scholar]
  27. Parish J. H., Kirby K. S. Reagents which reduce interactions between ribosomal RNA and rapidly labelled RNA from rat liver. Biochim Biophys Acta. 1966 Dec 21;129(3):554–562. doi: 10.1016/0005-2787(66)90070-0. [DOI] [PubMed] [Google Scholar]
  28. Peacock A. C., Dingman C. W. Molecular weight estimation and separation of ribonucleic acid by electrophoresis in agarose-acrylamide composite gels. Biochemistry. 1968 Feb;7(2):668–674. doi: 10.1021/bi00842a023. [DOI] [PubMed] [Google Scholar]
  29. Pegg A. E. Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone). Biochem J. 1973 Mar;132(3):537–540. doi: 10.1042/bj1320537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pegg A. E. Reactivity of analogues of S-adenosylmethionine in the enzymic synthesis of spermidine by mammalian tissues. Biochim Biophys Acta. 1969 Apr 1;177(2):361–364. [PubMed] [Google Scholar]
  31. Pegg A. E. Studies of the ethylation of rat liver transfer ribonucleic acid after administration of L-ethionine. Biochem J. 1972 Jun;128(1):59–68. doi: 10.1042/bj1280059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Perry R. P., Kelley D. E. The production of ribosomal RNA from high molecular weight precursors. 3. Hydrolysis of pre-ribosomal and ribosomal RNA by a 3'-OH specific exoribonuclease. J Mol Biol. 1972 Sep 28;70(2):265–279. doi: 10.1016/0022-2836(72)90538-4. [DOI] [PubMed] [Google Scholar]
  33. Perry R. P. The nucleolus and the synthesis of ribosomes. Prog Nucleic Acid Res Mol Biol. 1967;6:219–257. doi: 10.1016/s0079-6603(08)60528-0. [DOI] [PubMed] [Google Scholar]
  34. Ritossa F. M., Atwood K. C., Lindsley D. L., Spiegelman S. On the chromosomal distribution of DNA complementary to ribosomal and soluble RNA. Natl Cancer Inst Monogr. 1966 Dec;23:449–472. [PubMed] [Google Scholar]
  35. Shinozuka H., Goldblatt P. J., Farber E. The disorganization of hepatic cell nucleoli induced by ethionine and its reversal by adenine. J Cell Biol. 1968 Feb;36(2):313–328. doi: 10.1083/jcb.36.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shull K. H., McConomy J., Vogt M., Castillo A., Farber E. On the mechanism of induction of hepatic adenosine triphosphate deficiency by ethionine. J Biol Chem. 1966 Nov 10;241(21):5060–5070. [PubMed] [Google Scholar]
  37. Shull K. H., Villa-Trevino S. The effects of hadacidin and inosine on hepatic protein synthesis and adenosine triphosphate levels in ethionine-treated rats. Biochem Biophys Res Commun. 1964 Jun 1;16(2):101–105. doi: 10.1016/0006-291x(64)90343-2. [DOI] [PubMed] [Google Scholar]
  38. Stewart G. A., Farber E. The rapid acceleration of hepatic nuclear ribonucleic acid breakdown by actinomycin but not by ethionine. J Biol Chem. 1968 Sep 10;243(17):4479–4485. [PubMed] [Google Scholar]
  39. Tavitian A., Uretsky S. C., Acs G. Selective inhibition of ribosomal RNA synthesis in mammalian cells. Biochim Biophys Acta. 1968 Mar 18;157(1):33–43. doi: 10.1016/0005-2787(68)90261-x. [DOI] [PubMed] [Google Scholar]
  40. Timberlake W. E., Griffin D. H. Differential effects of analogs of cycloheximide on protein and RNA synthesis in Achlya. Biochim Biophys Acta. 1974 Apr 27;349(1):39–46. doi: 10.1016/0005-2787(74)90006-9. [DOI] [PubMed] [Google Scholar]
  41. VILLA-TREVINO S., SHULL K. H., FARBER E. The role of adenosine triphosphate deficiency in ethionine-induced inhibition of protein synthesis. J Biol Chem. 1963 May;238:1757–1763. [PubMed] [Google Scholar]
  42. Vaughan M. H., Jr, Soeiro R., Warner J. R., Darnell J. E., Jr The effects of methionine deprivation on ribosome synthesis in HeLa cells. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1527–1534. doi: 10.1073/pnas.58.4.1527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Verbin R. S., Goldblatt P. J., Farber E. The biochemical pathology of inhibition of protein synthesis in vivo. The effects of cycloheximide on hepatic parenchymal cell ultrastructure. Lab Invest. 1969 Jun;20(6):529–536. [PubMed] [Google Scholar]
  44. Villa-Trevino S., Shull K. H., Farber E. The inhibition of liver ribonucleic acid synthesis by ethionine. J Biol Chem. 1966 Oct 25;241(20):4670–4674. [PubMed] [Google Scholar]
  45. WYATT G. R. The purine and pyrimidine composition of deoxypentose nucleic acids. Biochem J. 1951 May;48(5):584–590. doi: 10.1042/bj0480584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Weiss J. W., Pitot H. C. Inhibition of ribosomal RNA maturation in Novikoff hepatoma cells by toyocamycin, tubercidin, and 6-thioguanosine. Cancer Res. 1974 Mar;34(3):581–587. [PubMed] [Google Scholar]
  47. Yu F. L., Feigelson P. The rapid turnover of RNA polymerase of rat liver nucleolus, and of its messenger RNA. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2833–2837. doi: 10.1073/pnas.69.10.2833. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES