The SFP1 controls translation termination in Saccharomyces cerevisiae via regulation of Sup35p (eRF3) level

Drozdova, Polina; Radchenko, Elina A.; Rogoza, Tatyana; Khokhrina, Maria; Mironova, L. N.

doi:10.1134/s0026893313010044

Cited by 4 publications

(8 citation statements)

References 30 publications

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“…Dissimilar to Sup35, no reproducible difference was shown for Sup45 levels, which also corroborates the previous findings (Drozdova et al . ) (Fig. B,C).…”

Section: Resultsmentioning

confidence: 81%

“…Increase in SUP35 expression in the [ psi − ] strain was previously shown during SFP1 over‐expression (Drozdova et al . ). Expression of the SFP1 gene under control of the inducible CUP1 promoter caused a severe growth defect in the strong [ PSI + ] background (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…B,C), which is consistent with the results obtained previously in the [ psi − ] strain (Drozdova et al . ). Dissimilar to Sup35, no reproducible difference was shown for Sup45 levels, which also corroborates the previous findings (Drozdova et al .…”

Section: Resultsmentioning

confidence: 97%

“…; Drozdova et al . ). In this work, we presented new evidence supporting the role of Sfp1 in the regulation of translation termination.…”

Section: Discussionmentioning

confidence: 97%

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SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

et al. 2016

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propagation. In this work, we identified SFP1 as a multicopy inducer of [PSI + ]-dependent lethality. Sfp1 is likely to up-regulate transcription of genes encoding release factors; however, its overproduction increases Sup35, but not Sup45 protein level. Using the synthetic lethality test, we compared the effects of SFP1 and SUP35 over-expression on the viability of [PSI + ] strains.Together with an observation that Sfp1 overproduction leads to an increased accumulation of Sup35 in [PSI + ] aggregates, we suggest that excess Sfp1 causes [PSI + ] toxicity. Even though SUP45 over-expression is known to compensate for the [PSI + ]-dependent lethality, it fails to do so when the lethality is caused by SFP1 over-expression. We discovered that the increased levels of Hsp40 chaperone Sis1 alleviate prion toxicity caused by either SFP1 or SUP35 over-expression and revert back to normal distribution of Sup35 between monomers and aggregate fractions. Finally, we showed that Sfp1 partially colocalizes with Sup35 aggregates, which may contribute to another mechanism of Sfp1-derived [PSI + ] prion toxicity. Introduction [PSI +], one of the best studied yeast prions, is formed by amyloid aggregates of the translation termination factor Sup35 (eRF3). Both translation termination factor genes SUP45 and SUP35 encoding eRF1 and eRF3, respectively, are essential in yeast Saccharomyces cerevisiae (see . The Sup35 protein consists of three domains. The Nproximal region (Sup35N), or prion-forming domain (PrD), is not essential for viability and translation termination (Ter-Avanesyan et al. 1993), but is required for [PSI + ] induction (Chernoff et al. 1992;Derkatch et al. 1996) and propagation (Ter-Avanesyan et al. 1994). The charged M (middle) region (Sup35M) is required for neither viability nor translation termination; however, it may influence [PSI + ] propagation. The C-proximal region (Sup35C) is required (and sufficient) for translation termination and cell viability; it also contains eRF1-interacting domain (see ], which is the prion form of the Rnq1 protein (Derkatch et al. 1997(Derkatch et al. , 2001).Malfunctioning of translation termination apparatus allows readthrough of stop codons leading to the suppression of nonsense mutations (see . It can be caused by a decrease in the level of functional Sup35 or Sup45 via different mechanisms. For example, the collection of sup45 and sup35 suppressor mutants includes viable nonsense mutants, in which the amount of eRF1 or ]-dependent toxicity during PIN4C over-expression (Yang et al. 2013(Yang et al. , 2014 ] cells. SFP1-fs induction in OT56 led to a statistically significant increase in both SUP35 and SUP45 mRNA levels (Fig. 1A). Quantitative RT-PCR showed a 1.51-and 1.50-fold increase in median mRNA levels of SUP35 and SUP45, respectively. We also confirmed an increase in SFP1 expression, because the median SFP1 mRNA level increased 2.96-fold (Fig. 1A).To determine whether SFP1 increases Sup35 and Sup45 production, we estimated the protein levels using Western blotting. How...

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“…Dissimilar to Sup35, no reproducible difference was shown for Sup45 levels, which also corroborates the previous findings (Drozdova et al . ) (Fig. B,C).…”

Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 97%

“…; Drozdova et al . ). In this work, we presented new evidence supporting the role of Sfp1 in the regulation of translation termination.…”

Section: Discussionmentioning

confidence: 97%

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SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

et al. 2016

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“…Loss of [ ISP + ] restores the initial efficiency of nonsense suppression. It is interesting to note that overexpression of SFP1 decreases the efficiency of nonsense suppression like [ ISP + ], even when it does not induce [ ISP + ] (Rogoza et al ., ; Drozdova et al ., ). The mechanism linking Sfp1p prionization to termination of translation still remains elusive, but overall our data suggest that [ ISP + ] might act like a mild overproduction of Sfp1p but not like inactivation of this protein.…”

Section: Discussionmentioning

confidence: 98%

Transcriptional response to the [ISP⁺] prion ofSaccharomyces cerevisiaediffers from that induced by the deletion of its structural gene,SFP1

et al. 2014

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Currently, several protein-based genetic determinants, or prions, are described in yeast, and several hundred prion candidates have been predicted. Importantly, many known and potential prion proteins regulate transcription; therefore, prion induction should affect gene expression. While it is generally believed that the prion phenotype should mimic the deletion phenotype, this rule has exceptions. Formed by the transcription factor Sfp1p, [ISP(+) ] is one such exception as the [ISP(+) ] and sfp1Δ strains differ in many phenotypic traits. These data suggest that effects of prion formation by a transcription factor and its absence may affect gene expression in a different way. However, studies addressing this issue are practically absent. Here, we explore how [ISP(+) ] affects gene expression and how these changes correspond to the effect of SFP1 deletion. Our data indicate that the [ISP(+) ]-related expression changes cannot be explained by the inactivation of Sfp1p. Remarkably, most Sfp1p targets are not affected in the [ISP(+) ] strain; instead, the genes upregulated in the [ISP(+) ] strain are enriched in Gcn4p and Aft1p targets. We propose that Sfp1p serves as a part of a regulatory complex, and the activity of this complex may be modulated differently by the absence or prionization of Sfp1p.

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Transcription Factors Mcm1 and Sfp1 May Affect [PSI+] Prion Phenotype by Altering the Expression of the SUP35 Gene

Matveenko,

Mikhailichenko,

Drozdova

et al. 2024

Microbiology Research

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Mcm1 is an essential Q/N-rich transcription factor. Q/N-rich proteins interact with each other, and many affect the [PSI+] prion formed by the translation termination factor Sup35 (eRF3). We found that transient MCM1 overexpression increased nonsense suppression in [PSI+] strains and SUP35 transcription. As we had discovered similar effects of another Q/N-rich transcription factor, Sfp1, here we focus on the roles of Mcm1 and Sfp1 in SUP35 expression, as well as on the effects of Sfp1 on the expression of the gene encoding another release factor, Sup45 (eRF1). Mutations in the SUP35 promoter showed that none of the potential Mcm1 binding sites affected the Sup35 protein level or nonsense suppression, even during MCM1 overexpression. Mcm1 itself neither formed aggregates in vivo nor affected Sup35 aggregation. In contrast, a mutation in the Sfp1-binding site decreased Sup35 production and [PSI+] toxicity of excess Sfp1. Mutation of the Sfp1 binding site in the SUP45 promoter lowered SUP45 expression and increased nonsense suppression even more drastically. Our data indicate that the mechanisms of Mcm1 and Sfp1 action differ. While Mcm1 seems unlikely to directly regulate SUP35 expression, Sfp1 appears to act through its binding sites and to directly activate SUP35 expression, which in turn may influence the [PSI+] prion phenotype and toxicity.

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The SFP1 controls translation termination in Saccharomyces cerevisiae via regulation of Sup35p (eRF3) level

Cited by 4 publications

References 30 publications

SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

Transcriptional response to the [ISP⁺] prion ofSaccharomyces cerevisiaediffers from that induced by the deletion of its structural gene,SFP1

Transcription Factors Mcm1 and Sfp1 May Affect [PSI+] Prion Phenotype by Altering the Expression of the SUP35 Gene

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The SFP1 controls translation termination in Saccharomyces cerevisiae via regulation of Sup35p (eRF3) level

Cited by 4 publications

References 30 publications

SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

Transcriptional response to the [ISP+] prion ofSaccharomyces cerevisiaediffers from that induced by the deletion of its structural gene,SFP1

Transcription Factors Mcm1 and Sfp1 May Affect [PSI+] Prion Phenotype by Altering the Expression of the SUP35 Gene

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Transcriptional response to the [ISP⁺] prion ofSaccharomyces cerevisiaediffers from that induced by the deletion of its structural gene,SFP1