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. 1978 Aug;5(8):2979–2989. doi: 10.1093/nar/5.8.2979

Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA).

M Vedel, M Robert-Géro, M Legraverend, F Lawrence, E Lederer
PMCID: PMC342220  PMID: 211491

Abstract

A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.

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Selected References

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

  1. BERGQUIST P. L., MATTHEWS R. E. Occurrence and distribution of methylated purines in the ribonucleic acids of subcellular fractions. Biochem J. 1962 Nov;85:305–313. doi: 10.1042/bj0850305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baliga B. S., Borek E., Weinstein I. B., Srinivasan P. R. Differences in the transfer RNA's of normal liver and Novikoff hepatoma. Proc Natl Acad Sci U S A. 1969 Mar;62(3):899–905. doi: 10.1073/pnas.62.3.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bona C., Robert-Gero M., Lederer E. Inhibition of mitogen induced blastogenesis by 5'-deoxy-5'-S-iso-butyl adenosine. Biochem Biophys Res Commun. 1976 May 17;70(2):622–629. doi: 10.1016/0006-291x(76)91093-7. [DOI] [PubMed] [Google Scholar]
  4. DISCHE Z. Qualitative and quantitative colorimetric determination of heptoses. J Biol Chem. 1953 Oct;204(2):983–997. [PubMed] [Google Scholar]
  5. Don S., Bachrach U. Polyamine metabolism in normal and in virus-transformed chick embryo fibroblasts. Cancer Res. 1975 Dec;35(12):3618–3622. [PubMed] [Google Scholar]
  6. GOLDE A., VIGIER P. Growth of Rous sarcoma virus and cells in nonconfluent chick embryo monolayers. Virology. 1961 Sep;15:36–46. doi: 10.1016/0042-6822(61)90074-5. [DOI] [PubMed] [Google Scholar]
  7. HAM R. G. An improved nutrient solution for diploid Chinese hamster and human cell lines. Exp Cell Res. 1963 Feb;29:515–526. doi: 10.1016/s0014-4827(63)80014-2. [DOI] [PubMed] [Google Scholar]
  8. Hacker B., Mandel L. R. Altered transfer RNA methylase patterns induced by an avian oncogenic virus. Biochim Biophys Acta. 1969 Sep 17;190(1):38–51. doi: 10.1016/0005-2787(69)90152-x. [DOI] [PubMed] [Google Scholar]
  9. Jank P., Gross H. J. Methyl-deficient mammalian transfer RNA: II. Homologous methylation in vitro of liver tRNA from normal and ethionine-fed rats: ethionine effect on 5-methyl-cytidine synthesis in vivo. Nucleic Acids Res. 1974 Oct;1(10):1259–1267. doi: 10.1093/nar/1.10.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klagsbrun M. Changes in the methylation of transfer RNA in vaccinia infected HeLa cells. Virology. 1971 Apr;44(1):153–167. doi: 10.1016/0042-6822(71)90162-0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Leboy P. S., Glick J. M. tRNA methyltransferases from rat liver. Differences in response of partially purified enzymes to polyamines and inorganic salts. Biochim Biophys Acta. 1976 Jun 2;435(1):30–38. doi: 10.1016/0005-2787(76)90188-x. [DOI] [PubMed] [Google Scholar]
  13. Lu L. W., Chiang G. H., Randerath K. Effects of DL-ethionine on mouse liver tRNA base composition. Nucleic Acids Res. 1976 Sep;3(9):2243–2253. doi: 10.1093/nar/3.9.2243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Munns T. W., Podratz K. C., Katzman P. A. A method for determination of the methylated constituents of transfer ribonucleic acid. Biochemistry. 1974 Oct 8;13(21):4409–4416. doi: 10.1021/bi00718a026. [DOI] [PubMed] [Google Scholar]
  15. Pegg A. E. Studies on inhibitors of mammalian tRNA methylases. FEBS Lett. 1971 Jul 15;16(1):13–16. doi: 10.1016/0014-5793(71)80672-5. [DOI] [PubMed] [Google Scholar]
  16. Pierré A., Richou M., Lawrence F., Robert-Géro M., Vigier P. Decreased rate of S-adenosyl-L-homocysteine metabolism: an early event related to transformation in cells infected with Rous sarcoma virus. Biochem Biophys Res Commun. 1977 Jun 6;76(3):813–819. doi: 10.1016/0006-291x(77)91573-x. [DOI] [PubMed] [Google Scholar]
  17. Raies A., Lawrence F., Robert-Gero M. Effect of 5'-deoxy-5'-S-isobutyl adenosine on polyoma virus replication. FEBS Lett. 1976 Dec 15;72(1):48–52. doi: 10.1016/0014-5793(76)80810-1. [DOI] [PubMed] [Google Scholar]
  18. Robert-Géro M., Lawrence F., Farrugia G., Berneman A., Blanchard P., Vigier P., Lederer E. Inhibition of virus-induced cell transformation by synthetic analogues of S-adenosyl homocysteine. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1242–1249. doi: 10.1016/s0006-291x(75)80363-9. [DOI] [PubMed] [Google Scholar]
  19. Sharma O. K., Loeb L. A. Methylation of transfer RNA during transformation of human lymphocytes by phytohemagglutinin. Biochem Biophys Res Commun. 1973 Jan 4;50(1):172–178. doi: 10.1016/0006-291x(73)91079-6. [DOI] [PubMed] [Google Scholar]
  20. Tsutsui E., Srinivasan P. R., Borek E. TRNA methylases in tumors of animal and human origin. Proc Natl Acad Sci U S A. 1966 Sep;56(3):1003–1009. doi: 10.1073/pnas.56.3.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wainfan E., Tscherne J. S., Maschio F. A., Balis M. E. Time dependence of ethionine-induced changes in rat liver transfer RNA methylation. Cancer Res. 1977 Mar;37(3):865–869. [PubMed] [Google Scholar]

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