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Nonstandard genetic codes and translation termination

Abstract

Genetic code is not universal. Various nonstandard versions of the code are known for some mitochondrial, prokaryotic, and eukaryotic genomes. The most common deviation is stop codon reassignment; i.e., a stop codon is decoded as a sense codon rather than as a signal for translation termination. Class 1 release factors (RFs: prokaryotic RF1 and RF2 and eukaryotic eRF1) recognize the stop codons and induce hydrolysis of peptidyl-tRNA in the ribosome. The specificity of class 1 RFs changes in organisms with a nonstandard code. The rare amino acids selenocysteine and pyrrolysine utilize essentially different decoding strategies. The review considers several hypotheses of the origin of nonstandard genetic codes. A new hypothesis is advanced, assuming a change in the specificity of class 1 RFs as a starting point for stop codon reassignment.

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References

  1. Soll D., RajBhandary U.L. 2006. The genetic code: Thawing the “frozen accident”. J. Biosci. 31, 459–463.

    Article  PubMed  CAS  Google Scholar 

  2. Osawa S., Jukes T.H., Watanabe K., Muto A. 1992. Recent evidence for evolution of the genetic code. Microbiol. Rev. 56, 229–264.

    PubMed  CAS  Google Scholar 

  3. Hao B., Gong W., Ferguson T.K., James C.M., Krzycki J.A., Chan M.K. 2002. A new UAG-encoded residue in the structure of a methanogen methyltransferase. Science. 296, 1462–1466.

    Article  PubMed  CAS  Google Scholar 

  4. Bock A., Forchhammer K., Heider J., Leinfelder W., Sawers G., Veprek B., Zinoni F. 1991. Selenocysteine: The 21st amino acid. Mol. Microbiol. 5, 515–520.

    Article  PubMed  CAS  Google Scholar 

  5. Kisselev L., Ehrenberg M., Frolova L. 2003. Termination of translation: Interplay of mRNA, rRNAs, and release factors? EMBO J. 22, 175–182.

    Article  PubMed  CAS  Google Scholar 

  6. Kisselev L.L., Buckingham R.H. 2000. Translational termination comes of age. Trends Biochem. Sci. 25, 561–566.

    Article  PubMed  CAS  Google Scholar 

  7. Chavatte L., Seit-Nebi A., Dubovaya V., Favre A. 2002. The invariant uridine of stop codons contacts the conserved NIKSR loop of human eRF1 in the ribosome. EMBO J. 21, 5302–5311.

    Article  PubMed  CAS  Google Scholar 

  8. Frolova L., Seit-Nebi A., Kisselev L. 2002. Highly conserved NIKS tetrapeptide is functionally essential in eukaryotic translation termination factor eRF1. RNA. 8, 129–136.

    Article  PubMed  CAS  Google Scholar 

  9. Bertram G., Bell H.A., Ritchie D.W., Fullerton G., Stansfield I. 2000. Terminating eukaryote translation: Domain 1 of release factor eRF1 functions in stop codon recognition. RNA. 6, 1236–1247.

    Article  PubMed  CAS  Google Scholar 

  10. Seit-Nebi A., Frolova L., Kisselev L. 2002. Conversion of omnipotent translation termination factor eRF1 into ciliate-like UGA-only unipotent eRF1. EMBO Rep. 3, 881–886.

    Article  PubMed  CAS  Google Scholar 

  11. Kolosov P., Frolova L., Seit-Nebi A., Dubovaya V., Kononenko A., Oparina N., Justesen J., Efimov A., Kisselev L. 2005. Invariant amino acids essential for decoding function of polypeptide release factor eRF1. Nucleic Acids Res. 33, 6418–6425.

    Article  PubMed  CAS  Google Scholar 

  12. Frolova L., Le Goff X., Zhouravleva G., Davydova E., Philippe M., Kisselev L. 1996. Eukaryotic polypeptide chain release factor eRF3 is an eRF1-and ribosome-dependent guanosine triphosphatase. RNA. 2, 334–341.

    PubMed  CAS  Google Scholar 

  13. Zavialov A.V., Buckingham R.H., Ehrenberg M. 2001. A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor RF3. Cell. 107, 115–124.

    Article  PubMed  CAS  Google Scholar 

  14. Alkalaeva E.Z., Pisarev A.V., Frolova L.Y., Kisselev L.L., Pestova T.V. 2006. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 125, 1125–1136.

    Article  PubMed  CAS  Google Scholar 

  15. Santos M.A., Moura G., Massey S.E., Tuite M.F. 2004. Driving change: The evolution of alternative genetic codes. Trends Genet. 20, 95–102.

    Article  PubMed  CAS  Google Scholar 

  16. Knight R.D., Freeland S.J., Landweber L.F. 2001. Rewiring the keyboard: Evolvability of the genetic code. Nature Rev. Genet. 2, 49–58.

    Article  CAS  PubMed  Google Scholar 

  17. Miranda I., Silva R., Santos M.A. 2006. Evolution of the genetic code in yeasts. Yeast. 23, 203–213.

    Article  PubMed  CAS  Google Scholar 

  18. Lee C.C., Timms K.M., Trotman C.N., Tate W.P. 1987. Isolation of a rat mitochondrial release factor: Accommodation of the changed genetic code for termination. J. Biol. Chem. 262, 3548–3552.

    PubMed  CAS  Google Scholar 

  19. Askarian-Amiri M.E., Pel H.J., Guevremont D., McCaughan K.K., Poole E.S., Sumpter V.G., Tate W.P. 2000. Functional characterization of yeast mitochondrial release factor 1. J. Biol. Chem. 275, 17,241–17,248.

    Article  CAS  Google Scholar 

  20. Heckman J.E., Sarnoff J., Alzner-DeWeerd B., Yin S., RajBhandary U.L. 1980. Novel features in the genetic code and codon reading patterns in Neurospora crassa mitochondria based on sequences of six mitochondrial tRNAs. Proc. Natl. Acad. Sci. USA. 77, 3159–3163.

    Article  PubMed  CAS  Google Scholar 

  21. Jukes T.H., Osawa S. 1990. The genetic code in mitochondria and chloroplasts. Experientia. 46, 1117–1126.

    Article  PubMed  CAS  Google Scholar 

  22. Yamao F., Muto A., Kawauchi Y., Iwami M., Iwagami S., Azumi Y., Osawa S. 1985. UGA is read as tryptophan in Mycoplasma capricolum. Proc. Natl. Acad. Sci. USA. 82, 2306–2309.

    Article  PubMed  CAS  Google Scholar 

  23. Inagaki Y., Bessho Y., Hori H., Osawa S. 1996. Cloning of the Mycoplasma capricolum gene encoding peptide-chain release factor. Gene. 169, 101–103.

    Article  PubMed  CAS  Google Scholar 

  24. Kim O.T., Yura K., Go N., Harumoto T. 2005. Newly sequenced eRF1s from ciliates: The diversity of stop codon usage and the molecular surfaces that are important for stop codon interactions. Gene. 346, 277–286.

    Article  PubMed  CAS  Google Scholar 

  25. Lozupone C.A., Knight R.D., Landweber L.F. 2001. The molecular basis of nuclear genetic code change in ciliates. Curr. Biol. 11, 65–74.

    Article  PubMed  CAS  Google Scholar 

  26. Tourancheau A.B., Tsao N., Klobutcher L.A., Pearlman R.E., Adoutte A. 1995. Genetic code deviations in the ciliates: Evidence for multiple and independent events. EMBO J. 14, 3262–3267.

    PubMed  CAS  Google Scholar 

  27. Prescott D.M. 1994. The DNA of ciliated protozoa. Microbiol Rev. 58, 233–267.

    PubMed  CAS  Google Scholar 

  28. Cohen J., Adoutte A. 1995. Why does the genetic code deviate so easily in ciliates? Biol. Cell. 85, 105–108.

    Article  PubMed  CAS  Google Scholar 

  29. Hanyu N., Kuchino Y., Nishimura S., Beier H. 1986. Dramatic events in ciliate evolution: Alteration of UAA and UAG termination codons to glutamine codons due to anticodon mutations in two Tetrahymena tRNAs. EMBO J. 5, 1307–1311.

    PubMed  CAS  Google Scholar 

  30. Horowitz S., Gorovsky M.A. 1985. An unusual genetic code in nuclear genes of Tetrahymena. Proc. Natl. Acad. Sci. USA. 82, 2452–2455.

    Article  PubMed  CAS  Google Scholar 

  31. Eisen J.A., Coyne R.S., Wu M., Wu D., Thiagarajan M., Wortman J.R., Badger J.H., Ren Q., Amedeo P., Jones K.M. et al. 2006. Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biol. 4, e286.

    Article  PubMed  CAS  Google Scholar 

  32. Ito K., Frolova L., Seit-Nebi A., Karamyshev A., Kisselev L., Nakamura Y. 2002. Omnipotent decoding potential resides in eukaryotic translation termination factor eRF1 of variant-code organisms and is modulated by the interactions of amino acid sequences within domain 1. Proc. Natl. Acad. Sci. USA. 99, 8494–8499.

    Article  PubMed  CAS  Google Scholar 

  33. Salas-Marco J., Fan-Minogue H., Kallmeyer A.K., Klobutcher L.A., Farabaugh P.J., Bedwell D.M. 2006. Distinct paths to stop codon reassignment by the variant-code organisms Tetrahymena and Euplotes. Mol. Cell Biol. 26, 438–447.

    Article  PubMed  CAS  Google Scholar 

  34. Preer J.R., Jr., Preer L.B., Rudman B.M., Barnett A.J. 1985. Deviation from the universal code shown by the gene for surface protein 51A in Paramecium. Nature. 314, 188–190.

    Article  PubMed  CAS  Google Scholar 

  35. Grimm M., Brunen-Nieweler C., Junker V., Heckmann K., Beier H. 1998. The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule. Nucleic Acids Res. 26, 4557–4565.

    Article  PubMed  CAS  Google Scholar 

  36. Hoffman D.C., Anderson R.C., DuBois M.L., Prescott D.M. 1995. Macronuclear gene-sized molecules of hypotrichs. Nucleic Acids Res. 23, 1279–1283.

    Article  PubMed  CAS  Google Scholar 

  37. Kervestin S., Frolova L., Kisselev L., Jean-Jean O. 2001. Stop codon recognition in ciliates: Euplotes release factor does not respond to reassigned UGA codon. EMBO Rep. 2, 680–684.

    Article  PubMed  CAS  Google Scholar 

  38. Chavatte L., Kervestin S., Favre A., Jean-Jean O. 2003. Stop codon selection in eukaryotic translation termination: Comparison of the discriminating potential between human and ciliate eRF1s. EMBO J. 22, 1644–1653.

    Article  PubMed  CAS  Google Scholar 

  39. Liang A., Brunen-Nieweler C., Muramatsu T., Kuchino Y., Beier H., Heckmann K. 2001. The ciliate Euplotes octocarinatus expresses two polypeptide release factors of the type eRF1. Gene. 262, 161–168.

    Article  PubMed  CAS  Google Scholar 

  40. Inagaki Y., Doolittle W.F. 2001. Class I release factors in ciliates with variant genetic codes. Nucleic Acids Res. 29, 921–927.

    Article  PubMed  CAS  Google Scholar 

  41. Kervestin S., Garnier O.A., Karamyshev A.L., Ito K., Nakamura Y., Meyer E., Jean-Jean O. 2002. Isolation and expression of two genes encoding eukaryotic release factor 1 from Paramecium tetraurelia. J. Eukaryot. Microbiol. 49, 374–382.

    Article  PubMed  CAS  Google Scholar 

  42. Ambrogelly A., Palioura S., Soll D. 2007. Natural expansion of the genetic code. Nature Chem. Biol. 3, 29–35.

    Article  CAS  Google Scholar 

  43. Allmang C., Krol A. 2006. Selenoprotein synthesis: UGA does not end the story. Biochimie. 88, 1561–1571.

    Article  PubMed  CAS  Google Scholar 

  44. Doronina V.A., Brown J.D. 2006. Non-canonical decoding events at stop codons in eukaryotes. Mol. Biol. 40, 731–741.

    Article  CAS  Google Scholar 

  45. Zhang Y., Baranov P.V., Atkins J.F., Gladyshev V.N. 2005. Pyrrolysine and selenocysteine use dissimilar decoding strategies. J. Biol. Chem. 280, 20,740–20,751.

    CAS  Google Scholar 

  46. Osawa S., Jukes T.H. 1995. On codon reassignment. J. Mol. Evol. 41, 247–249.

    Article  PubMed  CAS  Google Scholar 

  47. Andersson S.G., Kurland C.G. 1995. Genomic evolution drives the evolution of the translation system. Biochem. Cell Biol. 73, 775–787.

    Article  PubMed  CAS  Google Scholar 

  48. Andersson S.G., Kurland C.G. 1998. Reductive evolution of resident genomes. Trends Microbiol. 6, 263–268.

    Article  PubMed  CAS  Google Scholar 

  49. Inagaki Y., Bessho Y., Osawa S. 1993. Lack of peptiderelease activity responding to codon UGA in Mycoplasma capricolum. Nucleic Acids Res. 21, 1335–1338.

    Article  PubMed  CAS  Google Scholar 

  50. Schultz D.W., Yarus M. 1996. On malleability in the genetic code. J. Mol. Evol. 42, 597–601.

    Article  PubMed  CAS  Google Scholar 

  51. Yarus M., Schultz D.W. 1997. Further comments on codon reassignment. Response. J. Mol. Evol. 45, 3–6.

    Article  PubMed  CAS  Google Scholar 

  52. Gomes A.C., Costa T., Carreto L., Santos M.A. 2006. The molecular mechanism of evolution of changes in the genetic code. Mol. Biol. 40, 634–639.

    Article  CAS  Google Scholar 

  53. Beier H., Grimm M. 2001. Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Res. 29, 4767–4782.

    Article  PubMed  CAS  Google Scholar 

  54. Chavatte L., Frolova L., Laugaa P., Kisselev L., Favre A. 2003. Stop codons and UGG promote efficient binding of the polypeptide release factor eRF1 to the ribosomal A site. J. Mol. Biol. 331, 745–758.

    Article  PubMed  CAS  Google Scholar 

  55. Keeling P.J., Doolittle W.F. 1996. A non-canonical genetic code in an early diverging eukaryotic lineage. EMBO J. 15, 2285–2290.

    PubMed  CAS  Google Scholar 

  56. Keeling P.J., Leander B.S. 2003. Characterisation of a non-canonical genetic code in the oxymonad Streblomastix strix. J. Mol. Biol. 326, 1337–1349.

    Article  PubMed  CAS  Google Scholar 

  57. Giege R., Sissler M., Florentz C. 1998. Universal rules and idiosyncratic features in tRNA identity. Nucleic Acids Res. 26, 5017–5035.

    Article  PubMed  CAS  Google Scholar 

  58. Kimura M. 1980. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J. Mol. Evol. 16, 111–120.

    Article  PubMed  CAS  Google Scholar 

  59. Schultz D.W., Yarus M. 1994. Transfer RNA mutation and the malleability of the genetic code. J. Mol. Biol. 235, 1377–1380.

    Article  PubMed  CAS  Google Scholar 

  60. Bidou L., Stahl G., Hatin I., Namy O., Rousset J.P., Farabaugh P.J. 2000. Nonsense-mediated decay mutants do not affect programmed-1 frameshifting. RNA. 6, 952–961.

    Article  PubMed  CAS  Google Scholar 

  61. Ter-Avanesyan M.D., Kushnirov V.V. 1999. Prions: Infectious proteins with genetic properties. Biokhimiya. 64, 1382–1390.

    CAS  Google Scholar 

  62. True H.L., Lindquist S.L. 2000. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature. 407, 477–483.

    Article  PubMed  CAS  Google Scholar 

  63. Santos M.A., Cheesman C., Costa V., Moradas-Ferreira P., Tuite M.F. 1999. Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp. Mol. Microbiol. 31, 937–947.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to S. A. Lekomtsev.

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Original Russian Text © S.A. Lekomtsev, 2007, published in Molekulyarnaya Biologiya, 2007, Vol. 41, No. 6, pp. 964–972.

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Lekomtsev, S.A. Nonstandard genetic codes and translation termination. Mol Biol 41, 878–885 (2007). https://doi.org/10.1134/S0026893307060027

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