Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1997 Mar 3;16(5):1122–1134. doi: 10.1093/emboj/16.5.1122

The 'polysemous' codon--a codon with multiple amino acid assignment caused by dual specificity of tRNA identity.

T Suzuki 1, T Ueda 1, K Watanabe 1
PMCID: PMC1169711  PMID: 9118950

Abstract

In some Candida species, the universal CUG leucine codon is translated as serine. However, in most cases, the serine tRNAs responsible for this non-universal decoding (tRNA(Ser)CAG) accept in vitro not only serine, but also, to some extent, leucine. Nucleotide replacement experiments indicated that m1G37 is critical for leucylation activity. This finding was supported by the fact that the tRNA(Ser)CAGs possessing the leucylation activity always have m1G37, whereas that of Candida cylindracea, which possesses no leucylation activity, has A37. Quantification of defined aminoacetylated tRNAs in cells demonstrated that 3% of the tRNA(Ser)CAGs possessing m1G37 were, in fact, charged with leucine in vivo. A genetic approach using an auxotroph mutant of C.maltosa possessing this type of tRNA(Ser)CAG also suggested that the URA3 gene inactivated due to the translation of CUG as serine was rescued by a slight incorporation of leucine into the polypeptide, which demonstrated that the tRNA charged with multiple amino acids could participate in the translation. These findings provide the first evidence that two distinct amino acids are assigned by a single codon, which occurs naturally in the translation process of certain Candida species. We term this novel type of codon a 'polysemous codon'.

Full Text

The Full Text of this article is available as a PDF (504.9 KB).

Selected References

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

  1. Bare L., Bruce A. G., Gesteland R., Uhlenbeck O. C. Uridine-33 in yeast tRNA not essential for amber suppression. Nature. 1983 Oct 6;305(5934):554–556. doi: 10.1038/305554a0. [DOI] [PubMed] [Google Scholar]
  2. Boeke J. D., LaCroute F., Fink G. R. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. doi: 10.1007/BF00330984. [DOI] [PubMed] [Google Scholar]
  3. Crain P. F., McCloskey J. A. The RNA modification database. Nucleic Acids Res. 1996 Jan 1;24(1):98–99. doi: 10.1093/nar/24.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crick F. H. The origin of the genetic code. J Mol Biol. 1968 Dec;38(3):367–379. doi: 10.1016/0022-2836(68)90392-6. [DOI] [PubMed] [Google Scholar]
  5. Dix D. B., Wittenberg W. L., Uhlenbeck O. C., Thompson R. C. Effect of replacing uridine 33 in yeast tRNAPhe on the reaction with ribosomes. J Biol Chem. 1986 Aug 5;261(22):10112–10118. [PubMed] [Google Scholar]
  6. Donis-Keller H. Phy M: an RNase activity specific for U and A residues useful in RNA sequence analysis. Nucleic Acids Res. 1980 Jul 25;8(14):3133–3142. doi: 10.1093/nar/8.14.3133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Edelmann P., Gallant J. Mistranslation in E. coli. Cell. 1977 Jan;10(1):131–137. doi: 10.1016/0092-8674(77)90147-7. [DOI] [PubMed] [Google Scholar]
  8. Farabaugh P. J. Alternative readings of the genetic code. Cell. 1993 Aug 27;74(4):591–596. doi: 10.1016/0092-8674(93)90507-M. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gesteland R. F., Weiss R. B., Atkins J. F. Recoding: reprogrammed genetic decoding. Science. 1992 Sep 18;257(5077):1640–1641. doi: 10.1126/science.1529352. [DOI] [PubMed] [Google Scholar]
  10. Gold L. Posttranscriptional regulatory mechanisms in Escherichia coli. Annu Rev Biochem. 1988;57:199–233. doi: 10.1146/annurev.bi.57.070188.001215. [DOI] [PubMed] [Google Scholar]
  11. Ikemura T. Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and Escherichia coli with reference to the abundance of isoaccepting transfer RNAs. J Mol Biol. 1982 Jul 15;158(4):573–597. doi: 10.1016/0022-2836(82)90250-9. [DOI] [PubMed] [Google Scholar]
  12. Inoue H., Hayase Y., Iwai S., Ohtsuka E. Sequence-dependent hydrolysis of RNA using modified oligonucleotide splints and RNase H. FEBS Lett. 1987 May 11;215(2):327–330. doi: 10.1016/0014-5793(87)80171-0. [DOI] [PubMed] [Google Scholar]
  13. Kawaguchi Y., Honda H., Taniguchi-Morimura J., Iwasaki S. The codon CUG is read as serine in an asporogenic yeast Candida cylindracea. Nature. 1989 Sep 14;341(6238):164–166. doi: 10.1038/341164a0. [DOI] [PubMed] [Google Scholar]
  14. Keith G., Gilham P. T. Stepwise degradation of polyribonucleotides. Biochemistry. 1974 Aug 13;13(17):3601–3606. doi: 10.1021/bi00714a031. [DOI] [PubMed] [Google Scholar]
  15. Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. doi: 10.1128/mr.47.1.1-45.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurland C. G. Translational accuracy and the fitness of bacteria. Annu Rev Genet. 1992;26:29–50. doi: 10.1146/annurev.ge.26.120192.000333. [DOI] [PubMed] [Google Scholar]
  17. Leinfelder W., Zehelein E., Mandrand-Berthelot M. A., Böck A. Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine. Nature. 1988 Feb 25;331(6158):723–725. doi: 10.1038/331723a0. [DOI] [PubMed] [Google Scholar]
  18. Lin S. X., Baltzinger M., Remy P. Fast kinetic study of yeast phenylalanyl-tRNA synthetase: role of tRNAPhe in the discrimination between tyrosine and phenylalanine. Biochemistry. 1984 Aug 28;23(18):4109–4116. doi: 10.1021/bi00313a015. [DOI] [PubMed] [Google Scholar]
  19. Lloyd A. T., Sharp P. M. Evolution of codon usage patterns: the extent and nature of divergence between Candida albicans and Saccharomyces cerevisiae. Nucleic Acids Res. 1992 Oct 25;20(20):5289–5295. doi: 10.1093/nar/20.20.5289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murgola E. J. tRNA, suppression, and the code. Annu Rev Genet. 1985;19:57–80. doi: 10.1146/annurev.ge.19.120185.000421. [DOI] [PubMed] [Google Scholar]
  21. Normanly J., Abelson J. tRNA identity. Annu Rev Biochem. 1989;58:1029–1049. doi: 10.1146/annurev.bi.58.070189.005121. [DOI] [PubMed] [Google Scholar]
  22. Normanly J., Ogden R. C., Horvath S. J., Abelson J. Changing the identity of a transfer RNA. Nature. 1986 May 15;321(6067):213–219. doi: 10.1038/321213a0. [DOI] [PubMed] [Google Scholar]
  23. Ohama T., Suzuki T., Mori M., Osawa S., Ueda T., Watanabe K., Nakase T. Non-universal decoding of the leucine codon CUG in several Candida species. Nucleic Acids Res. 1993 Aug 25;21(17):4039–4045. doi: 10.1093/nar/21.17.4039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Osawa S., Jukes T. H., Watanabe K., Muto A. Recent evidence for evolution of the genetic code. Microbiol Rev. 1992 Mar;56(1):229–264. doi: 10.1128/mr.56.1.229-264.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parker J., Precup J. Mistranslation during phenylalanine starvation. Mol Gen Genet. 1986 Jul;204(1):70–74. doi: 10.1007/BF00330189. [DOI] [PubMed] [Google Scholar]
  26. Pesole G., Lotti M., Alberghina L., Saccone C. Evolutionary origin of nonuniversal CUGSer codon in some Candida species as inferred from a molecular phylogeny. Genetics. 1995 Nov;141(3):903–907. doi: 10.1093/genetics/141.3.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pütz J., Florentz C., Benseler F., Giegé R. A single methyl group prevents the mischarging of a tRNA. Nat Struct Biol. 1994 Sep;1(9):580–582. doi: 10.1038/nsb0994-580. [DOI] [PubMed] [Google Scholar]
  28. Rose M., Grisafi P., Botstein D. Structure and function of the yeast URA3 gene: expression in Escherichia coli. Gene. 1984 Jul-Aug;29(1-2):113–124. doi: 10.1016/0378-1119(84)90172-0. [DOI] [PubMed] [Google Scholar]
  29. Santos M. A., Tuite M. F. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res. 1995 May 11;23(9):1481–1486. doi: 10.1093/nar/23.9.1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schimmel P. Aminoacyl tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem. 1987;56:125–158. doi: 10.1146/annurev.bi.56.070187.001013. [DOI] [PubMed] [Google Scholar]
  31. Schultz D. W., Yarus M. Transfer RNA mutation and the malleability of the genetic code. J Mol Biol. 1994 Feb 4;235(5):1377–1380. doi: 10.1006/jmbi.1994.1094. [DOI] [PubMed] [Google Scholar]
  32. Schön A., Kannangara C. G., Gough S., Söll D. Protein biosynthesis in organelles requires misaminoacylation of tRNA. Nature. 1988 Jan 14;331(6152):187–190. doi: 10.1038/331187a0. [DOI] [PubMed] [Google Scholar]
  33. Sugiyama H., Ohkuma M., Masuda Y., Park S. M., Ohta A., Takagi M. In vivo evidence for non-universal usage of the codon CUG in Candida maltosa. Yeast. 1995 Jan;11(1):43–52. doi: 10.1002/yea.320110106. [DOI] [PubMed] [Google Scholar]
  34. Takagi M., Kawai S., Chang M. C., Shibuya I., Yano K. Construction of a host-vector system in Candida maltosa by using an ARS site isolated from its genome. J Bacteriol. 1986 Aug;167(2):551–555. doi: 10.1128/jb.167.2.551-555.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ueda T., Suzuki T., Yokogawa T., Nishikawa K., Watanabe K. Unique structure of new serine tRNAs responsible for decoding leucine codon CUG in various Candida species and their putative ancestral tRNA genes. Biochimie. 1994;76(12):1217–1222. doi: 10.1016/0300-9084(94)90052-3. [DOI] [PubMed] [Google Scholar]
  36. Wakita K., Watanabe Y., Yokogawa T., Kumazawa Y., Nakamura S., Ueda T., Watanabe K., Nishikawa K. Higher-order structure of bovine mitochondrial tRNA(Phe) lacking the 'conserved' GG and T psi CG sequences as inferred by enzymatic and chemical probing. Nucleic Acids Res. 1994 Feb 11;22(3):347–353. doi: 10.1093/nar/22.3.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wang Y. Y., Lyttle M. H., Borer P. N. Enzymatic and NMR analysis of oligoribonucleotides synthesized with 2'-tert-butyldimethylsilyl protected cyanoethylphosphoramidite monomers. Nucleic Acids Res. 1990 Jun 11;18(11):3347–3352. doi: 10.1093/nar/18.11.3347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. White T. C., Andrews L. E., Maltby D., Agabian N. The "universal" leucine codon CTG in the secreted aspartyl proteinase 1 (SAP1) gene of Candida albicans encodes a serine in vivo. J Bacteriol. 1995 May;177(10):2953–2955. doi: 10.1128/jb.177.10.2953-2955.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yarus M. tRNA identity: a hair of the dogma that bit us. Cell. 1988 Dec 2;55(5):739–741. doi: 10.1016/0092-8674(88)90127-4. [DOI] [PubMed] [Google Scholar]
  40. Yokogawa T., Suzuki T., Ueda T., Mori M., Ohama T., Kuchino Y., Yoshinari S., Motoki I., Nishikawa K., Osawa S. Serine tRNA complementary to the nonuniversal serine codon CUG in Candida cylindracea: evolutionary implications. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7408–7411. doi: 10.1073/pnas.89.16.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zimmer T., Schunck W. H. A deviation from the universal genetic code in Candida maltosa and consequences for heterologous expression of cytochromes P450 52A4 and 52A5 in Saccharomyces cerevisiae. Yeast. 1995 Jan;11(1):33–41. doi: 10.1002/yea.320110105. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES