Programmed translational frameshifting

A second mechanism acts at the level of translation elongation and involves programmed translational frameshifting between two consecutive open reading frames (Fig 1.33.1). Typically a -1 frameshift is observed in which the translating ribosome slides one base upstream and resumes in the alternative phase. This generally occurs at the position of so-called slippery codons in a heptanucleotide sequence of the type X XXZ ZZN in phase 0 (where the bases paired with the anticodon are shown as triplets) which is read as XXX ZZZ N in the shifted -1 phase (Fig 1.33.1) (see e.g. (Chandler & Fayet, 1993), (Farabaugh, 1996, Farabaugh, 1997), (Gesteland & Atkins, 1996), http://recode.genetics.utah.edu/). The sequence A AAA AAG is a common example of this type of heptanucleotide. Ribosomal shifting of this type is stimulated by structures in the mRNA which tend to impede the progression of the ribosome such as potential ribosome binding sites upstream or secondary structures (stem-loop structures and pseudoknots) downstream of the slippery codons (Farabaugh, 1997). Translational control of transposition by frameshifting has been demonstrated both for IS1 (Sekine & Ohtsubo, 1989`) (Escoubas, et al., 1991), and for members of the IS3 family (Fig 1.33.2) ((Polard, et al., 1991); see also (Chandler & Fayet, 1993) (Fayet & Prère, 2010)) but may also occur in several other IS elements (see for example IS5 and IS630 families). For IS1 and members of the IS3 family, the upstream frame appears to carry a DNA recognition domain whereas the downstream frame encodes the catalytic site. While the product of the upstream frame alone acts as a modulator of activity, presumably by binding to the IR sequences, frameshifting assembles both domains into a single protein, the Tpase, which directs the cleavages and strand transfer necessary for mobility of the element. The frameshifting frequency is thus critical in determining overall transposition activity. Although it has yet to be explored in detail, frameshifting could be influenced by host physiology thus coupling transposition activity to the state of the host cell.

References :

• Chandler M & Fayet O (1993) Translational frameshifting in the control of transposition in bacteria. Mol Microbiol 7: 497-503.
• Escoubas JM, Prere MF, Fayet O, Salvignol I, Galas D, Zerbib D & Chandler M (1991) Translational control of transposition activity of the bacterial insertion sequence IS1. Embo J 10: 705-712.
• Farabaugh PJ (1996) Programmed translational frameshifting. Microbiol.Rev. 60: 103-134.
• Farabaugh PJ (1997) Programmed Alternative Reading of the Genetic Code. R.G.Landes Company, Austin.
• Fayet O & Prère M-F (2010) Programmed Ribosomal −1 Frameshifting as a Tradition: The Bacterial Transposable Elements of the IS3 Family. . Recoding: Expansion of Decoding Rules Enriches Gene Expression, Vol. 24 (Atkins JF & Gesteland R, eds.), pp. 259-280. Springer, New York and Heidelberg.
• Gesteland RF & Atkins JF (1996) Recoding: dynamic reprogramming of translation. Annu.Rev.Biochem. 65: 741-768.
• Polard P, Prère MF, Chandler M & Fayet O (1991) Programmed translational frameshifting and initiation at an AUU codon in gene expression of bacterial insertion sequence IS911. J Mol Biol 222: 465-477.
• Sekine Y & Ohtsubo E (1989) Frameshifting is required for production of the transposase encoded by insertion sequence 1. Proc Natl Acad Sci U S A 86: 4609-4613.