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Home page > Thematics > Physiological roles of recoding > Frameshifting and yeast prion

Regulation of OAZ1 gene by [PSI+]

24 January 2011

Yeast Prion

Prion proteins are a specific class of amyloidogenic proteins, first described by Stanley B. Prusiner. These prions are infectious proteins, able to adopt a structural conformation that differs from that of the normal protein. This conformational change is then propagated among other molecules of the same protein.

Prion proteins also exist in fungi (in the yeast Saccharomyces cerevisiae and the filamentous fungus Podospora anserina), where they control heritable traits. These organisms have been used successfully to investigate the induction, formation and propagation phases of prion fibres. Yeast prions were first identified as non-Mendelian traits inherited through the cytoplasm.

These prions, called [URE3] and [PSI+], arise from self-replicating conformations of proteins encoded by chromosomal genes URE2 and SUP35 respectively. Definitive evidence of this has been provided by the demonstration that [PSI+] can be induced by infecting yeast with pure prion protein and that different conformations of stable Sup35 amyloids induce different [PSI+] variants. This proof of principle has also been demonstrated with the yeast [URE3] and [PIN+] prions, and the [Het-s] prion from P. anserina.

[PSI+] is the prion form of the eukaryotic release factor 3 (eRF3) encoded by the SUP35 gene in S. cerevisiae. The conformational change impairs the termination activity of eRF3 and consequently increases readthrough of stop codon (complete inactivation is lethal). Many phenotypes are associated with the appearance of [PSI+] and are linked with a defect in termination. However, whether [PSI+] causes a selective disadvantage or induces phenotype plasticity remains unclear. The absence of [PSI+] in wild yeasts is suggestive of a detrimental role for [PSI+], consistent with a potential defect in translation termination. However, this detrimental function could be counterbalanced by the transient presence of [PSI+] during stressful periods, facilitating the rapid adaptation of cells in a fluctuating environment. This would be consistent with the conservation of the eRF3 PFD and of its capacity to switch into a prion form over the past one hundred million years.

Prion and recoding

Nucleotides upstream and downstream from the stop codon have a profound impact on termination efficiency. Thus, in the presence of [PSI+], not all termination codons will be subject to readthrough. Indeed, the number of genes affected by the presence of [PSI+] is unknown.

JPEG - 30.7 kb
Polyamines regulation
The antizyme protein is regulated by a +1 frameshifting event, which acts as a sensor of polyamine levels in the cell.

We recently provided important insight on this issue by demonstrating that a [PSI+]-induced defect in translation termination stimulates expression of the OAZ1 gene, leading to a decrease of polyamines in the cell [1]. This gene uses a programmed “shifty-stop” to regulate its own expression at the translational level. In the presence of [PSI+], translation termination is defective, leading to an increased pausing time of the ribosome at the stop codon. This longer pause stimulates +1 frameshifting, allowing a tRNA to enter the +1 frame. The increase in Oaz1p (antizyme) enhances ODC degradation and causes a drop in polyamine levels. This change in polyamine level explains half of the [PSI+]-induced phenotypes.


Prion and recoding

We are continuing this work on prion, to determine whether other genes could be also regulated by [PSI+].


[1] Epigenetic control of polyamines by the prion [PSI+]. Namy O, Galopier A, Martini C, Matsufuji S, Fabret C, Rousset JP. Nat Cell Biol. 2008. 10(9):1069-75