Logo of embojLink to Publisher's site
EMBO J. Mar 15, 1999; 18(6): 1427–1434.
PMCID: PMC1171232

How translational accuracy influences reading frame maintenance.

Abstract

Most missense errors have little effect on protein function, since they only exchange one amino acid for another. However, processivity errors, frameshifting or premature termination result in a synthesis of an incomplete peptide. There may be a connection between missense and processivity errors, since processivity errors now appear to result from a second error occurring after recruitment of an errant aminoacyl-tRNA, either spontaneous dissociation causing premature termination or translational frameshifting. This is clearest in programmed translational frameshifting where the mRNA programs errant reading by a near-cognate tRNA; this error promotes a second frameshifting error (a dual-error model of frameshifting). The same mechanism can explain frameshifting by suppressor tRNAs, even those with expanded anticodon loops. The previous model that suppressor tRNAs induce quadruplet translocation now appears incorrect for most, and perhaps for all of them. We suggest that the 'spontaneous' tRNA-induced frameshifting and 'programmed' mRNA-induced frameshifting use the same mechanism, although the frequency of frameshifting is very different. This new model of frameshifting suggests that the tRNA is not acting as the yardstick to measure out the length of the translocation step. Rather, the translocation of 3 nucleotides may be an inherent feature of the ribosome.

Full Text

The Full Text of this article is available as a PDF (302K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Atkins JF, Weiss RB, Thompson S, Gesteland RF. Towards a genetic dissection of the basis of triplet decoding, and its natural subversion: programmed reading frame shifts and hops. Annu Rev Genet. 1991;25:201–228. [PubMed]
  • Barak Z, Lindsley D, Gallant J. On the mechanism of leftward frameshifting at several hungry codons. J Mol Biol. 1996 Mar 8;256(4):676–684. [PubMed]
  • Belcourt MF, Farabaugh PJ. Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site. Cell. 1990 Jul 27;62(2):339–352. [PubMed]
  • Blinkowa AL, Walker JR. Programmed ribosomal frameshifting generates the Escherichia coli DNA polymerase III gamma subunit from within the tau subunit reading frame. Nucleic Acids Res. 1990 Apr 11;18(7):1725–1729. [PMC free article] [PubMed]
  • Bossi L, Roth JR. Four-base codons ACCA, ACCU and ACCC are recognized by frameshift suppressor sufJ. Cell. 1981 Aug;25(2):489–496. [PubMed]
  • Bossi L, Smith DM. Suppressor sufJ: a novel type of tRNA mutant that induces translational frameshifting. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6105–6109. [PMC free article] [PubMed]
  • Calos MP, Miller JH. Genetic and sequence analysis of frameshift mutations induced by ICR-191. J Mol Biol. 1981 Nov 25;153(1):39–64. [PubMed]
  • Caplan AB, Menninger JR. Tests of the ribosomal editing hypothesis: amino acid starvation differentially enhances the dissociation of peptidyl-tRNA from the ribosome. J Mol Biol. 1979 Nov 5;134(3):621–637. [PubMed]
  • Craigen WJ, Caskey CT. Expression of peptide chain release factor 2 requires high-efficiency frameshift. Nature. 1986 Jul 17;322(6076):273–275. [PubMed]
  • CRICK FH, BARNETT L, BRENNER S, WATTS-TOBIN RJ. General nature of the genetic code for proteins. Nature. 1961 Dec 30;192:1227–1232. [PubMed]
  • Curran JF, Yarus M. Rates of aminoacyl-tRNA selection at 29 sense codons in vivo. J Mol Biol. 1989 Sep 5;209(1):65–77. [PubMed]
  • Czworkowski J, Moore PB. The elongation phase of protein synthesis. Prog Nucleic Acid Res Mol Biol. 1996;54:293–332. [PubMed]
  • Dabrowski M, Spahn CM, Nierhaus KH. Interaction of tRNAs with the ribosome at the A and P sites. EMBO J. 1995 Oct 2;14(19):4872–4882. [PMC free article] [PubMed]
  • Donly BC, Edgar CD, Adamski FM, Tate WP. Frameshift autoregulation in the gene for Escherichia coli release factor 2: partly functional mutants result in frameshift enhancement. Nucleic Acids Res. 1990 Nov 25;18(22):6517–6522. [PMC free article] [PubMed]
  • Farabaugh PJ. Programmed translational frameshifting. Microbiol Rev. 1996 Mar;60(1):103–134. [PMC free article] [PubMed]
  • Farabaugh PJ, Zhao H, Vimaladithan A. A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: frameshifting without tRNA slippage. Cell. 1993 Jul 16;74(1):93–103. [PubMed]
  • Flower AM, McHenry CS. The gamma subunit of DNA polymerase III holoenzyme of Escherichia coli is produced by ribosomal frameshifting. Proc Natl Acad Sci U S A. 1990 May;87(10):3713–3717. [PMC free article] [PubMed]
  • Gaber RF, Culbertson MR. Frameshift suppression in Saccharomyces cerevisiae. IV. New suppressors among spontaneous co-revertants of the Group II his4-206 and leu 2-3 frameshift mutations. Genetics. 1982 Jul-Aug;101(3-4):345–367. [PMC free article] [PubMed]
  • Gaber RF, Culbertson MR. Codon recognition during frameshift suppression in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Oct;4(10):2052–2061. [PMC free article] [PubMed]
  • Gabriel K, Schneider J, McClain WH. Functional evidence for indirect recognition of G.U in tRNA(Ala) by alanyl-tRNA synthetase. Science. 1996 Jan 12;271(5246):195–197. [PubMed]
  • Gallant J, Lindsley D. Ribosome frameshifting at hungry codons: sequence rules, directional specificity and possible relationship to mobile element behaviour. Biochem Soc Trans. 1993 Nov;21(4):817–821. [PubMed]
  • Holley RW. Structure of an alanine transfer ribonucleic acid. JAMA. 1965 Nov 22;194(8):868–871. [PubMed]
  • Hüttenhofer A, Weiss-Brummer B, Dirheimer G, Martin RP. A novel type of + 1 frameshift suppressor: a base substitution in the anticodon stem of a yeast mitochondrial serine-tRNA causes frameshift suppression. EMBO J. 1990 Feb;9(2):551–558. [PMC free article] [PubMed]
  • Ikemura T, Ozeki H. Codon usage and transfer RNA contents: organism-specific codon-choice patterns in reference to the isoacceptor contents. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):1087–1097. [PubMed]
  • Jakubowski H, Goldman E. Editing of errors in selection of amino acids for protein synthesis. Microbiol Rev. 1992 Sep;56(3):412–429. [PMC free article] [PubMed]
  • Jørgensen F, Adamski FM, Tate WP, Kurland CG. Release factor-dependent false stops are infrequent in Escherichia coli. J Mol Biol. 1993 Mar 5;230(1):41–50. [PubMed]
  • Kurland CG. Translational accuracy and the fitness of bacteria. Annu Rev Genet. 1992;26:29–50. [PubMed]
  • Matzke AJ, Barta A, Kuechler E. Mechanism of translocation: relative arrangement of tRNA and mRNA on the ribosome. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5110–5114. [PMC free article] [PubMed]
  • Menninger JR. Ribosome editing and the error catastrophe hypothesis of cellular aging. Mech Ageing Dev. 1977 Mar-Apr;6(2):131–142. [PubMed]
  • Moazed D, Noller HF. Intermediate states in the movement of transfer RNA in the ribosome. Nature. 1989 Nov 9;342(6246):142–148. [PubMed]
  • Newmark RA, Cantor CR. Nuclear magnetic resonance study of the interactions of guanosine and cytidine in dimethyl sulfoxide. J Am Chem Soc. 1968 Aug 28;90(18):5010–5017. [PubMed]
  • Nierhaus KH. The allosteric three-site model for the ribosomal elongation cycle: features and future. Biochemistry. 1990 May 29;29(21):4997–5008. [PubMed]
  • O'Connor M. tRNA imbalance promotes -1 frameshifting via near-cognate decoding. J Mol Biol. 1998 Jun 19;279(4):727–736. [PubMed]
  • O'Mahony DJ, Mims BH, Thompson S, Murgola EJ, Atkins JF. Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7979–7983. [PMC free article] [PubMed]
  • Peter K, Lindsley D, Peng L, Gallant JA. Context rules of rightward overlapping reading. New Biol. 1992 May;4(5):520–526. [PubMed]
  • Qian Q, Björk GR. Structural alterations far from the anticodon of the tRNAProGGG of Salmonella typhimurium induce +1 frameshifting at the peptidyl-site. J Mol Biol. 1997 Nov 14;273(5):978–992. [PubMed]
  • Qian Q, Li JN, Zhao H, Hagervall TG, Farabaugh PJ, Björk GR. A new model for phenotypic suppression of frameshift mutations by mutant tRNAs. Mol Cell. 1998 Mar;1(4):471–482. [PubMed]
  • Randerath E, Gupta RC, Chia LL, Chang SH, Randerath K. Yeast tRNA Leu UAG. Purification, properties and determination of the nucleotide sequence by radioactive derivative methods. Eur J Biochem. 1979 Jan 2;93(1):79–94. [PubMed]
  • Riddle DL, Carbon J. Frameshift suppression: a nucleotide addition in the anticodon of a glycine transfer RNA. Nat New Biol. 1973 Apr 25;242(121):230–234. [PubMed]
  • Skopek TR, Hutchinson F. Frameshift mutagenesis of lambda prophage by 9-aminoacridine, proflavin and ICR-191. Mol Gen Genet. 1984;195(3):418–423. [PubMed]
  • Sroga GE, Nemoto F, Kuchino Y, Björk GR. Insertion (sufB) in the anticodon loop or base substitution (sufC) in the anticodon stem of tRNA(Pro)2 from Salmonella typhimurium induces suppression of frameshift mutations. Nucleic Acids Res. 1992 Jul 11;20(13):3463–3469. [PMC free article] [PubMed]
  • Thompson RC. EFTu provides an internal kinetic standard for translational accuracy. Trends Biochem Sci. 1988 Mar;13(3):91–93. [PubMed]
  • Tsuchihashi Z, Kornberg A. Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2516–2520. [PMC free article] [PubMed]
  • Tsuchihashi Z, Brown PO. Sequence requirements for efficient translational frameshifting in the Escherichia coli dnaX gene and the role of an unstable interaction between tRNA(Lys) and an AAG lysine codon. Genes Dev. 1992 Mar;6(3):511–519. [PubMed]
  • Tucker SD, Murgola EJ, Pagel FT. Missense and nonsense suppressors can correct frameshift mutations. Biochimie. 1989 Jun;71(6):729–739. [PubMed]
  • Vimaladithan A, Farabaugh PJ. Special peptidyl-tRNA molecules can promote translational frameshifting without slippage. Mol Cell Biol. 1994 Dec;14(12):8107–8116. [PMC free article] [PubMed]
  • Weiss RB, Gallant JA. Frameshift suppression in aminoacyl-tRNA limited cells. Genetics. 1986 Apr;112(4):727–739. [PMC free article] [PubMed]
  • Weiss RB, Dunn DM, Atkins JF, Gesteland RF. Slippery runs, shifty stops, backward steps, and forward hops: -2, -1, +1, +2, +5, and +6 ribosomal frameshifting. Cold Spring Harb Symp Quant Biol. 1987;52:687–693. [PubMed]
  • Weiss RB, Dunn DM, Dahlberg AE, Atkins JF, Gesteland RF. Reading frame switch caused by base-pair formation between the 3' end of 16S rRNA and the mRNA during elongation of protein synthesis in Escherichia coli. EMBO J. 1988 May;7(5):1503–1507. [PMC free article] [PubMed]
  • Weissenbach J, Dirheimer G, Falcoff R, Sanceau J, Falcoff E. Yeast tRNALeu (anticodon U--A--G) translates all six leucine codons in extracts from interferon treated cells. FEBS Lett. 1977 Oct 1;82(1):71–76. [PubMed]
  • Wilson KS, Noller HF. Molecular movement inside the translational engine. Cell. 1998 Feb 6;92(3):337–349. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...