Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jan;75(1):275–279. doi: 10.1073/pnas.75.1.275

Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation.

P C Tai, B J Wallace, B D Davis
PMCID: PMC411229  PMID: 343106

Abstract

The induction of misreading by streptomycin in vitro, previously observed with synthetic messengers, is now demonstrated with natural (endogenous or viral) messenger by the use of extracts of temperature sensitive mutants lacking Glu--tRNA or Val--tRNA synthetase. With chain-elongating but noninitiating ribosomes (i.e., purified polysomes) deprived of an aminoacyl--tRNA, streptomycin and other aminoglycosides, over a wide range of concentrations, stimulate incorporation. With ribosomes initiating in the presence of streptomycin stimulation is also observed but it is restricted, just like phenotypic suppression in cells, to very low streptomycin concentrattions which evidently allow some ribosomes to initiate and later encounter them in the course of chain elongation. The stimulation is accompanied by an increase in the size of the products; hence, it is evidently due to substitution of an incorrect aminoacyl--tRNA for a missing one. The test introduced here also has revealed a misreading effect of streptomycin on resistant ribosomes. In addition, significant intrinsic misreading was observed without streptomycin, indicating that under optimal conditions for in vitro protein synthesis an empty codon is frequently read by an incorrect aminoacyl--tRNA.

Full text

PDF
275

Selected References

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

  1. Anderson W. F., Gorini L., Breckenridge L. Role of ribosomes in streptomycin-activated suppression. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1076–1083. doi: 10.1073/pnas.54.4.1076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blomberg C. A kinetic recognition process for tRNA at the ribosome. J Theor Biol. 1977 May 21;66(2):307–325. doi: 10.1016/0022-5193(77)90174-6. [DOI] [PubMed] [Google Scholar]
  3. Chang F. N., Flaks J. G. Binding of dihydrostreptomycin to Escherichia coli ribosomes: characteristics and equilibrium of the reaction. Antimicrob Agents Chemother. 1972 Oct;2(4):294–307. doi: 10.1128/aac.2.4.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DAVIES J., GILBERT W., GORINI L. STREPTOMYCIN, SUPPRESSION, AND THE CODE. Proc Natl Acad Sci U S A. 1964 May;51:883–890. doi: 10.1073/pnas.51.5.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davies J., Davis B. D. Misreading of ribonucleic acid code words induced by aminoglycoside antibiotics. The effect of drug concentration. J Biol Chem. 1968 Jun 25;243(12):3312–3316. [PubMed] [Google Scholar]
  7. Davies J., Gorini L., Davis B. D. Misreading of RNA codewords induced by aminoglycoside antibiotics. Mol Pharmacol. 1965 Jul;1(1):93–106. [PubMed] [Google Scholar]
  8. EIDLIC L., NEIDHARDT F. C. PROTEIN AND NUCLEIC ACID SYNTHESIS IN TWO MUTANTS OF ESCHERICHIA COLI WITH TEMPERATURE-SENSITIVE AMINOACYL RIBONUCLEIC ACID SYNTHETASES. J Bacteriol. 1965 Mar;89:706–711. doi: 10.1128/jb.89.3.706-711.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GORINI L., KATAJA E. PHENOTYPIC REPAIR BY STREPTOMYCIN OF DEFECTIVE GENOTYPES IN E. COLI. Proc Natl Acad Sci U S A. 1964 Mar;51:487–493. doi: 10.1073/pnas.51.3.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorini L. Ribosomal discrimination of tRNAs. Nat New Biol. 1971 Dec 29;234(52):261–264. doi: 10.1038/newbio234261a0. [DOI] [PubMed] [Google Scholar]
  11. Hopfield J. J. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4135–4139. doi: 10.1073/pnas.71.10.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kaplan S., Atherly A. G., Barrett A. Synthesis of stable RNA in stringent Escherichia coli cells in the absence of charged transfer RNA. Proc Natl Acad Sci U S A. 1973 Mar;70(3):689–692. doi: 10.1073/pnas.70.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kurland C. G., Rigler R., Ehrenberg M., Blomberg C. Allosteric mechanism for codon-dependent tRNA selection on ribosomes. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4248–4251. doi: 10.1073/pnas.72.11.4248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kurland C. G. Structure and function of the bacterial ribosome. Annu Rev Biochem. 1977;46:173–200. doi: 10.1146/annurev.bi.46.070177.001133. [DOI] [PubMed] [Google Scholar]
  15. Lake J. A. Aminoacyl-tRNA binding at the recognition site is the first step of the elongation cycle of protein synthesis. Proc Natl Acad Sci U S A. 1977 May;74(5):1903–1907. doi: 10.1073/pnas.74.5.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Luzzatto L., Apirion D., Schlessinger D. Streptomycin action: greater inhibition of Escherichia coli ribosome function with exogenous than with endogenous messenger ribonucleic acid. J Bacteriol. 1969 Jul;99(1):206–209. doi: 10.1128/jb.99.1.206-209.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Modolell J., Davis B. D. Rapid inhibition of polypeptide chain extension by streptomycin. Proc Natl Acad Sci U S A. 1968 Dec;61(4):1279–1286. doi: 10.1073/pnas.61.4.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ninio J. A semi-quantitative treatment of missense and nonsense suppression in the strA and ram ribosomal mutants of Escherichia coli. Evaluation of some molecular parameters of translation in vivo. J Mol Biol. 1974 Apr 5;84(2):297–313. doi: 10.1016/0022-2836(74)90586-5. [DOI] [PubMed] [Google Scholar]
  19. Ninio J. Kinetic amplification of enzyme discrimination. Biochimie. 1975;57(5):587–595. doi: 10.1016/s0300-9084(75)80139-8. [DOI] [PubMed] [Google Scholar]
  20. Schwartz J. H. An effect of streptomycin on the biosynthesis of the coat protein of coliphage f2 by extract of E. coli. Proc Natl Acad Sci U S A. 1965 May;53(5):1133–1140. doi: 10.1073/pnas.53.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shapiro A. L., Viñuela E., Maizel J. V., Jr Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem Biophys Res Commun. 1967 Sep 7;28(5):815–820. doi: 10.1016/0006-291x(67)90391-9. [DOI] [PubMed] [Google Scholar]
  22. Tai P. C., Wallace B. J., Herzog E. L., Davis B. D. Properties of initiation-free polysomes of Escherichia coli. Biochemistry. 1973 Feb;12(4):609–615. doi: 10.1021/bi00728a007. [DOI] [PubMed] [Google Scholar]
  23. Thompson R. C., Stone P. J. Proofreading of the codon-anticodon interaction on ribosomes. Proc Natl Acad Sci U S A. 1977 Jan;74(1):198–202. doi: 10.1073/pnas.74.1.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. VAN KNIPPENBERGP, VAN CLAASENJ, GRIJM-VOS M., VELDSTRA H., BOSCH L. STIMULATION AND INHIBITION OF POLYPEPTIDE SYNTHESIS BY STREPTOMYCIN IN RIBOSOMAL SYSTEMS OF ESCHERICHIA COLI, PROGRAMMED WITH VARIOUS MESSENGERS. Biochim Biophys Acta. 1965 Mar 15;95:461–473. doi: 10.1016/0005-2787(65)90192-9. [DOI] [PubMed] [Google Scholar]
  25. Wallace B. J., Tai P. C., Herzog E. L., Davis B. D. Partial inhibition of polysomal ribosomes of Escherichia coli by streptomycin. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1234–1237. doi: 10.1073/pnas.70.4.1234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weber K. Amino acid sequence studies on the tryptic peptides of the coat protein of the bacteriophage R17. Biochemistry. 1967 Oct;6(10):3144–3154. doi: 10.1021/bi00862a023. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES