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Review
. 2004 Feb;10(2):221-30.
doi: 10.1261/rna.5122604.

P-site tRNA is a crucial initiator of ribosomal frameshifting

Pavel V Baranov  1 , Raymond F Gesteland, John F Atkins
Affiliations
Review

P-site tRNA is a crucial initiator of ribosomal frameshifting

Pavel V Baranov et al. RNA. 2004 Feb.

Abstract

The expression of some genes requires a high proportion of ribosomes to shift at a specific site into one of the two alternative frames. This utilized frameshifting provides a unique tool for studying reading frame control. Peptidyl-tRNA slippage has been invoked to explain many cases of programmed frameshifting. The present work extends this to other cases. When the A-site is unoccupied, the P-site tRNA can be repositioned forward with respect to mRNA (although repositioning in the minus direction is also possible). A kinetic model is presented for the influence of both, the cognate tRNAs competing for overlapping codons in A-site, and the stabilities of P-site tRNA:mRNA complexes in the initial and new frames. When the A-site is occupied, the P-site tRNA can be repositioned backward. Whether frameshifting will happen depends on the ability of the A-site tRNA to subsequently be repositioned to maintain physical proximity of the tRNAs. This model offers an alternative explanation to previously published mechanisms of programmed frameshifting, such as out-of-frame tRNA binding, and a different perspective on simultaneous tandem tRNA slippage.

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Figures

FIGURE 1.
FIGURE 1.
Simplified scheme of the translation elongation cycle. Two main types of ribosomal frameshifting are distinguished depending on the phase of the elongation cycle where tRNA repositioning occurs.
FIGURE 2.
FIGURE 2.
Energetic profile of P-site codon:anticodon complexes. P-site tRNA dissociated from mRNA is considered as an activation complex for P-site tRNA repositioning. Transition from a tRNA: mRNA complex with the codon in the initial frame to where the codon is in an alternative frame, can be achieved in two ways: (1) by increasing the rate constant of the forward reaction (higher energy of the initial complex); and (2) by decreasing the rate constant of the reverse reaction (lower energy of the new complex).
FIGURE 3.
FIGURE 3.
Graphical representation of the affect of several parameters on frameshifting efficiency in Ty1. (A) The effect of concentration of “in-frame” A-site tRNA. (B) The effect of concentration of “out-of-frame” tRNA. (C,D) The effects of the rate constants for the repositioning of P-site tRNA, k1 and k2, depend on “instability” of the initial P-site codon:anticodon complex and “instability” of the P-site tRNA complex with the +1-frame codon, respectively.
See this image and copyright information in PMC

References

    1. Atkins, J.F., Gesteland, R.F., Reid, B.R., and Anderson, C.W. 1979. Normal tRNAs promote ribosomal frameshifting. Cell 18: 1119–1131. - PubMed
    1. Atkins, J.F., Herr, A.J., Massire, C., O’Connor, M., Ivanov, I., and Gesteland, R.F. 2000. Poking a hole in the sanctity of the triplet code: Inferences for framing. In The ribosome: Structure, function, antibiotics and cellular interactions (eds. R.A. Garrett et al.), pp. 369–383. ASM Press, Washington, DC.
    1. Baranov, P.V., Gesteland, R.F., and Atkins, J.F. 2002a. Recoding: Translational bifurcations in gene expression. Gene 286: 187–201. - PubMed
    1. ———. 2002b. Release factor 2 frameshifting sites in different bacteria. EMBO Rep. 3: 373–377. - PMC - PubMed
    1. Baranov, P.V., Gurvich, O.L., Hammer, A.W., Gesteland, R.F., and Atkins, J.F. 2003. Recode 2003. Nucleic Acids Res. 31: 87–89. - PMC - PubMed

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