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. 2006 Nov;1(11):521-527.
doi: 10.1128/microbe.1.521.1.

Programmed Ribosomal Frameshifting Goes Beyond Viruses: Organisms from all three kingdoms use frameshifting to regulate gene expression, perhaps signaling a paradigm shift

Affiliations

Programmed Ribosomal Frameshifting Goes Beyond Viruses: Organisms from all three kingdoms use frameshifting to regulate gene expression, perhaps signaling a paradigm shift

Jonathan D Dinman. Microbe Wash DC. 2006 Nov.
No abstract available

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Figures

Fig. 1
Fig. 1
General concept of programmed ribosomal frameshifting. Ribosomes translating mRNA encounter the frameshift signal (hatched box). One feature of the signal induces the ribosome to pause. During this time, a second feature facilitates the shift. Frameshifting frequency is a function of kinetic partitioning between the rates of the forward reaction, i.e. remaining in frame, and rates of the side reaction, i.e. shifting into a new frame.
Fig 2
Fig 2
Fig 2A Autoregulation of Release Factor 2 (RF2) synthesis by programmed +1 ribosomal frameshifting. The open reading frame encoding RF2, the translation termination factor that recognizes the UGA and UAA termination codons, contains an in-frame UGA codon that must be bypassed for complete translation of the protein. Low levels of RF2 promote inefficient recognition of the UGA codon. Ribosome pausing at this site enables base-pairing between an upstream Shine-Dalgarno like sequence, repositioning the ribosome to the +1 reading frame. The resulting +1 PRF event results in RF2 production. As RF2 levels rise, UGA codon recognition increases, dampening frameshifting and RF2 production. Figure 2B Autoregulation of polyamine synthesis by programmed +1 ribosomal frameshifting. Ornithine decarboxylase (ODC) converts ornithine into putrescine, the substrate for all subsequent polyamine biosynthesis. Excess levels of polyamines stimulate +1 programmed ribosomal frameshifting on the antizyme mRNA, resulting in synthesis of antizyme (AZ). This enzyme sequesters ODC, triggering ODC degradation by the 26S proteosome. AZ is not degraded, but is recycled into the pathway.
Fig. 3
Fig. 3
Programmed −1 ribosomal frameshifting in dnaX is stimulated by three cis-acting mRNA elements. A downstream stem-loop structure induces ribosomal pausing over the “slippery” AAAAAAG heptamer. Like RF2, an upstream Shine-Dalgarno like sequence repositions the ribosome, but by 1 base in the 5′ (−1) direction. The tRNAs that were paired to AAA and AAG in the incoming frame are shifted to base pair with AAA and AAA codons in the −1 frame. Normally, the τ subunit of DNA Polymerase III is synthesized. However, consequent to the frameshift, redirection of ribosomes to the −1 frame UGA codon results in production of the γ subunit.
Figure 4
Figure 4
Model of mRNA suicide by frameshifting. If a translating ribosome bypasses the −1 PRF signal, it processes to the normal termination codon, and the mRNA is stable (normal translation at right). In contrast, a PRF event would direct ribosomes to a premature termination codon, targeting the mRNA for rapid degradation via the nonsense-mediated mRNA decay pathway (NMD).

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