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EMBO J. 1997 Mar 3; 16(5): 1122–1134.
PMCID: PMC1169711

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


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'.

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Selected References

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  • Bare L, Bruce AG, Gesteland R, Uhlenbeck OC. Uridine-33 in yeast tRNA not essential for amber suppression. Nature. 1983 Oct 6;305(5934):554–556. [PubMed]
  • Boeke JD, LaCroute F, Fink GR. 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. [PubMed]
  • Crain PF, McCloskey JA. The RNA modification database. Nucleic Acids Res. 1996 Jan 1;24(1):98–99. [PMC free article] [PubMed]
  • Crick FH. The origin of the genetic code. J Mol Biol. 1968 Dec;38(3):367–379. [PubMed]
  • Dix DB, Wittenberg WL, Uhlenbeck OC, Thompson RC. Effect of replacing uridine 33 in yeast tRNAPhe on the reaction with ribosomes. J Biol Chem. 1986 Aug 5;261(22):10112–10118. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Edelmann P, Gallant J. Mistranslation in E. coli. Cell. 1977 Jan;10(1):131–137. [PubMed]
  • Farabaugh PJ. Alternative readings of the genetic code. Cell. 1993 Aug 27;74(4):591–596. [PubMed]
  • Gesteland RF, Weiss RB, Atkins JF. Recoding: reprogrammed genetic decoding. Science. 1992 Sep 18;257(5077):1640–1641. [PubMed]
  • Gold L. Posttranscriptional regulatory mechanisms in Escherichia coli. Annu Rev Biochem. 1988;57:199–233. [PubMed]
  • Parker J, Precup J. Mistranslation during phenylalanine starvation. Mol Gen Genet. 1986 Jul;204(1):70–74. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Santos MA, Tuite MF. 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. [PMC free article] [PubMed]
  • Keith G, Gilham PT. Stepwise degradation of polyribonucleotides. Biochemistry. 1974 Aug 13;13(17):3601–3606. [PubMed]
  • Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. [PMC free article] [PubMed]
  • Kurland CG. Translational accuracy and the fitness of bacteria. Annu Rev Genet. 1992;26:29–50. [PubMed]
  • 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. [PubMed]
  • Leinfelder W, Zehelein E, Mandrand-Berthelot MA, Böck A. Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine. Nature. 1988 Feb 25;331(6158):723–725. [PubMed]
  • Schön A, Kannangara CG, Gough S, Söll D. Protein biosynthesis in organelles requires misaminoacylation of tRNA. Nature. 1988 Jan 14;331(6152):187–190. [PubMed]
  • Lin SX, 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. [PubMed]
  • Schultz DW, Yarus M. Transfer RNA mutation and the malleability of the genetic code. J Mol Biol. 1994 Feb 4;235(5):1377–1380. [PubMed]
  • Lloyd AT, Sharp PM. 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. [PMC free article] [PubMed]
  • Murgola EJ. tRNA, suppression, and the code. Annu Rev Genet. 1985;19:57–80. [PubMed]
  • Normanly J, Ogden RC, Horvath SJ, Abelson J. Changing the identity of a transfer RNA. Nature. 1986 May 15;321(6067):213–219. [PubMed]
  • Normanly J, Abelson J. tRNA identity. Annu Rev Biochem. 1989;58:1029–1049. [PubMed]
  • Sugiyama H, Ohkuma M, Masuda Y, Park SM, 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Takagi M, Kawai S, Chang MC, 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Osawa S, Jukes TH, Watanabe K, Muto A. Recent evidence for evolution of the genetic code. Microbiol Rev. 1992 Mar;56(1):229–264. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Wang YY, Lyttle MH, Borer PN. Enzymatic and NMR analysis of oligoribonucleotides synthesized with 2'-tert-butyldimethylsilyl protected cyanoethylphosphoramidite monomers. Nucleic Acids Res. 1990 Jun 11;18(11):3347–3352. [PMC free article] [PubMed]
  • White TC, Andrews LE, 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. [PMC free article] [PubMed]
  • Yarus M. tRNA identity: a hair of the dogma that bit us. Cell. 1988 Dec 2;55(5):739–741. [PubMed]
  • Yokogawa T, Suzuki T, Ueda T, Mori M, Ohama T, Kuchino Y, Yoshinari S, Motoki I, Nishikawa K, Osawa S, et al. 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. [PMC free article] [PubMed]
  • Zimmer T, Schunck WH. 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. [PubMed]

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