TY - JOUR

T1 - Distinct Mechanisms of Phenotypic Effects of Inactivation and Prionization of Swi1 Protein in Saccharomyces cerevisiae

AU - Antonets, K S

AU - Kliver, S F

AU - Polev, D E

AU - Shuvalova, A R

AU - Andreeva, E A

AU - Inge-Vechtomov, S G

AU - Nizhnikov, A A

PY - 2017

Y1 - 2017

N2 - Prions are proteins that under the same conditions can exist in two or more conformations, and at least one of the conformations has infectious properties. The prionization of a protein is typically accompanied by its functional inactivation due to sequestration of monomers by the prion aggregates. The most of prions has been identified in the yeast Saccharomyces cerevisiae. One of them is [SWI+], a prion isoform of the Swi1 protein, which is a component of the evolutionarily conserved chromatin remodeling complex SWI/SNF. Earlier, it was shown that the prionization of [SWI+] induces a nonsense suppression, which leads to weak growth of the [SWI+] strains containing mutant variants of the SUP35 gene and the nonsense allele ade1-14UGA on selective medium without adenine. This effect occurs because of [SWI+] induction that causes a decrease in the amount of the SUP45 mRNA. Strains carrying the SWI1 deletion exhibit significantly higher suppression of the ade1-14UGA nonsense mutation than the [SWI+] strains. In the present study, we identified genes whose expression is altered in the background of the SWI1 deletion using RNA sequencing. We found that the ade1-14UGA suppression in the swi1Δ strains is caused by an increase in the expression of this mutant allele of the ADE1 gene. At the same time, the SUP45 expression level in the swi1Δ strains does not significantly differ from the expression level of this gene in the [swi-] strains. Thus, we have shown that the phenotypic effects of Swi1 prionization and deletion are mediated by different molecular mechanisms. Based on these data, we have concluded that the prionization of proteins is not only unequal to their inactivation, but also can lead to the acquisition of novel phenotypic effects and functions.

AB - Prions are proteins that under the same conditions can exist in two or more conformations, and at least one of the conformations has infectious properties. The prionization of a protein is typically accompanied by its functional inactivation due to sequestration of monomers by the prion aggregates. The most of prions has been identified in the yeast Saccharomyces cerevisiae. One of them is [SWI+], a prion isoform of the Swi1 protein, which is a component of the evolutionarily conserved chromatin remodeling complex SWI/SNF. Earlier, it was shown that the prionization of [SWI+] induces a nonsense suppression, which leads to weak growth of the [SWI+] strains containing mutant variants of the SUP35 gene and the nonsense allele ade1-14UGA on selective medium without adenine. This effect occurs because of [SWI+] induction that causes a decrease in the amount of the SUP45 mRNA. Strains carrying the SWI1 deletion exhibit significantly higher suppression of the ade1-14UGA nonsense mutation than the [SWI+] strains. In the present study, we identified genes whose expression is altered in the background of the SWI1 deletion using RNA sequencing. We found that the ade1-14UGA suppression in the swi1Δ strains is caused by an increase in the expression of this mutant allele of the ADE1 gene. At the same time, the SUP45 expression level in the swi1Δ strains does not significantly differ from the expression level of this gene in the [swi-] strains. Thus, we have shown that the phenotypic effects of Swi1 prionization and deletion are mediated by different molecular mechanisms. Based on these data, we have concluded that the prionization of proteins is not only unequal to their inactivation, but also can lead to the acquisition of novel phenotypic effects and functions.

KW - Alleles

KW - Chromosomal Proteins, Non-Histone

KW - Chromosomes

KW - Mutagenesis

KW - Peptide Termination Factors

KW - RNA, Fungal

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Sequence Analysis, RNA

KW - Transcription Factors

KW - Journal Article

U2 - 10.1134/S0006297917100078

DO - 10.1134/S0006297917100078

M3 - Article

C2 - 29037135

VL - 82

SP - 1147

EP - 1157

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 10

ER -