PSI (prion)

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[PSI+] was first identified by Cox as a modifier of some types of translational suppression of mutant genes. The initial discovery of [PSI+] was made in a strain auxotrophic for the amino acid adenine due to a nonsense mutation ^[1] Further investigation found that [PSI+] is the misfolded form of Sup35, which is an important factor for translation termination during protein synthesis ^[2]. It is believed that [PSI+] causes suppression of nonsense mutations by sequestering functional Sup35 in non-functional aggregates, thereby allowing stop codon readthrough. [PIN+], in turn, is the misfolded form of the protein Rnq1. However, the normal function of this protein is unknown to date. It is of note that for the induction of most variants of [PSI+], the presence of [PIN+] is required. Though reasons for this are poorly understood, it is suggested that [PIN+] aggregates may act as “seeds” for the polymerization of [PSI+] ^[3]. Two modified versions of Sup35 have been created that can induce [PSI+] in the absence of [PIN+] when overexpressed. One version was created by digestion of the gene with BalI, which results in a protein consisting of only the M and N portions of Sup35 ^[4]. The other is a fusion of Sup35NM with HPR, a human membrane receptor protein.

Laboratories commonly identify [PSI+] by growth of a strain auxotrophic for adenine on media lacking adenine, similar to that used by Cox et al. These strains cannot synthesize adenine due to a nonsense mutation in one of the enzymes involved in biosynthetic pathway. When the strain is grown on yeast-extract/dextrose/peptone media (YPD), the blocked pathway results in buildup of a red-colored intermediate compound, which is exported from the cell due to its toxicity. Hence, color is an alternative method of identifying [PSI+] -- [PSI+] strains are white or pinkish in color, and [psi-] strains are red. A third method of identifying [PSI+] is by the presence of Sup35 in the pelleted fraction of cellular lysate.

[edit] References

1. ^ Cox, B. S., M. F. Tuite and C. S. McLaughlin (1988). "The [PSI+]-Factor of Yeast - a Problem in Inheritance". Yeast 4, 159–178
2. ^ Paushkin, S. V., V. V. Kushnirov, V. N. Smirnov and M. D. Ter-Avanesyan (1996). "Propagation of the yeast prion-like [PSI+] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor". EMBO (European Molecular Biology Organization) Journal 15, 3127–3134
3. ^ Chernoff, Y. O. (2001). "Mutation processes at the protein level: Is Lamarck back?". Mutation Research 488, 39–64
4. ^ Derkatch, I. L., M. E. Bradley, P. Zhou, Y. O. Chernoff and S. W. Liebman (1997). "Genetic and Environmental Factors Affecting the de novo Appearance of the [PSI+] Prion in Saccharomyces cerevisiae". Genetics 147 507–519