Gene Expression: Frameshifting


Ribosomes shift reading frames at high levels at specific places in the decoding of a minority of messenger ribonucleic acid (RNA)s in probably all organisms. This frameshifting serves a regulatory function or is used to synthesize more than one product from a coding sequence.

Keywords: genetic code; frameshift; recoding; ribosomes

Figure 1.

The required programmed +1 frameshifting in decoding the Escherichia coli gene for polypeptide chain release factor 2. The availability of release factor 2 governs the efficiency with which CUU decoding tRNALeu shifts from pairing with CUU to the overlapping +1 frame UUU to permit synthesis of more release factor 2. Pairing of the anti‐Shine–Dalgarno sequence near the 3′ end of 16S ribosomal RNA of translating ribosome with a complementary sequence just before the shift site is important for efficient frameshifting.

Figure 2.

The programmed –1 frameshifting in decoding Escherichia coli dnaX resulting in the synthesis of two subunits of DNA polymerase III. Tandem slippage at the A6G heptamer is stimulated by the 5′ ribosomal RNA:messenger RNA interaction and 3′ stem–loop shown. The ribosomes that shift frame decode one amino acid from the −1 frame, denoted by the orange colour at the C‐terminus of the γ product, before terminating translation at the UGA stop codon marked in red.

Figure 3.

Programmed frameshifting in decoding human antizyme 1 as a sensor of cellular polyamine levels for an autoregulatory circuit. A 5′ element (green), a stop codon (UGA in red) and a 3′ pseudoknot stimulate frameshifting at the UCC U shift site in a polyamine‐dependent manner. Ribosomes that do not frameshift terminate at the UGA stop codon, marked red, to synthesize only the product of the zero frame, marked blue.

Figure 4.

Rescue of a ribosome stuck at the end of a broken or incomplete messenger RNA (mRNA) by its transfer to an internal coding sequence of transfer messenger RNA (tmRNA). After resuming protein synthesis by translation of tmRNA, the ribosome quickly encounters a stop codon which causes termination of protein synthesis. It permits dissociation of the ribosome from mRNA and so future use of its component subunits.



Baranov PV, Gurvich OL, Hammer AW, Gesteland RF and Atkins JF (2003) Recode 2003. Nucleic Acids Research 31: 87–89.

Baril M, Dulude D, Gendron K, Lemay G and Brakier‐Gingras L (2003) Efficiency of a programmed −1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M. RNA 9: 1246–1253.

Barry JK and Miller WA (2002) A −1 ribosomal frameshift element that requires base pairing across four kilobases suggests a mechanism of regulating ribosome and replicase traffic on a viral RNA. Proceedings of the National Academy of Sciences of the USA 99: 11133–11138.

Bekaert M, Atkins JF and Baranov PV (2006) ARFA: a program for annotating bacterial release factor genes, including prediction of programmed ribosomal frameshifting. Bioinformatics 22: 2463–2465.

Brierley I and Pennell S (2001) Structure and function of the stimulatory RNAs involved in programmed eukaryotic −1 ribosomal frameshifting. Cold Spring Harbor Symposia Quantitative Biology 66: 233–248.

Brierley I, Rolley NJ, Jenner AJ and Inglis SC (1991) Mutational analysis of the RNA pseudoknot component of a Coronavirus frameshifting signal. Journal of Molecular Biology 220: 889–902.

Chen X, Kang H, Shen LX et al. (1996) A characteristic bent conformation of RNA pseudoknots promotes –1 frameshifting during translation of retroviral RNA. Journal of Molecular Biology 260: 479–483.

Cornish PV, Stammler SN and Giedroc DP (2006) The global structures of a wild‐type and poorly functional plant luteoviral mRNA pseudoknot are essentially identical. RNA 12: 1–11.

Craigen WJ, Cook RG, Tate WP and Caskey CT (1985) Bacterial peptide chain release factors: conserved primary structure and possible frameshift regulation of release factor. Proceedings of the National Academy of Sciences of the USA 82: 3616–3620.

Farabaugh PJ, Zhao H and Vimaladithan A (1993) A novel programmed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: frameshifting without tRNA slippage. Cell 74: 93–103.

Gramstat A, Prufer D and Rohde W (1994) The nucleic acid‐binding zinc finger protein of potato virus M is translated by internal initiation as well as by ribosomal frameshifting involving a shifty stop codon and a novel mechanism of P‐site slippage. Nucleic Acids Research 22: 3911–3917.

Griffiths A, Link MA, Furness CL and Coen DM (2006) Low‐level expression and reversion both contribute to reactivation of herpes simplex drug‐resistant mutants with mutations on homopolymeric sequences in thymidine kinase. Journal of Virology 80: 6568–6574.

Henderson CM, Anderson CB and Howard MT (2006) Antisense‐induced ribosomal frameshifting. Nucleic Acids Research 34: 4302–4310.

Jacks T, Madhani THD, Masiarz FR and Varmus HE (1988) Signals for ribosomal frameshifting in the Rous sarcoma virus gag‐pol region. Cell 55: 447–458.

Keiler KC, Waller PRH and Sauer RT (1996) Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271: 990–993.

Matsufuji S, Matsufuji T, Miyazaki Y et al. (1995) Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell 80: 51–60.

Namy O, Moran SJ, Stuart DI, Gilbert RJ and Brierley I (2006) A mechanical explanation for RNA pseudoknot function in programmed ribosomal frameshifting. Nature 441: 244–247.

Peltz SW, Hammell AB, Cui Y et al. (1999) Ribosomal protein L3 mutants alter translational fidelity and promote rapid loss of the yeast killer virus. Molecular and Cellular Biology 19: 384–391.

Su L, Chen L, Egli M, Berger JM and Rich A (1999) Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot. Nature Structural Biology 6: 285–292.

Sundararajan A, Michaud WA, Qian Q, Stahl G and Farabaugh PJ (1999) Near‐cognate peptidyl‐tRNAs promote +1 programmed translational frameshifting in yeast. Molecular Cell 4: 1005–1015.

Toulouse A, Au‐yeung F, Gaspar C et al. (2005) Ribosome frameshifting on MJD‐1 transcripts with long CAG tracts. Human Molecular Genetics 14: 2649–2660.

Tsuchihashi Z and Brown PO (1992) Sequence requirements for efficient translational frameshifting in the Escherichia coli dnaX gene and the role of an unstable interaction between tRNALys and an AAG lysine codon. Genes and Development 6: 511–519.

Weiss RB, Dunn DM, Dahlberg AE, Atkins JF and Gesteland RF (1988) 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 Journal 7: 1503–1507.

Zook MB, Howard MT, Sinnathamby G, Atkins JF and Eisenlohr LC (2006) Epitopes derived by incidental frameshifting give rise to a protective CTL response. Journal of Immunology 176: 6928–6934.

Further Reading

Dreher TW and Miller WA (2006) Translational control in positive strand RNA plant viruses. Virology 344: 185–197.

Gesteland RF and Atkins JF (1996) Recoding: dynamic reprogramming of translation. Annual Review of Biochemistry 65: 741–768.

Namy O, Rousset JP, Napthine S and Brierley I (2004) Reprogrammed genetic decoding in cellular gene expression. Molecular Cell 13: 157–168.

Stahl G, Ben Salem S, Li Z et al. (2001) Programmed +1 translational frameshifting in the yeast Saccharomyces cerevisiae results from disruption of translational error correction. Cold Spring Harbour Symposia Quantitative Biology 66: 249–258.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Atkins, John F, and Gesteland, Raymond F(Apr 2007) Gene Expression: Frameshifting. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001498.pub2]