Novel Non-Mendelian Determinant Involved in the Control of Translation Accuracy in <i>Saccharomyces cerevisiae</i>

Volkov, Kirill V.; Aksenova, Anna Y.; Soom, Malle J; Osipov, Kirill V; Svitin, Anton; Kurischko, Cornelia; Shkundina, Irina S; Ter‐Avanesyan, Michael D.; Inge-Vechtomov, Sergey G.; Mironova, L. N.

doi:10.1093/genetics/160.1.25

Cited by 85 publications

(17 citation statements)

References 51 publications

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“…Moreover, recruitment of Sfp1 to polyQ aggregates could contribute to reduced Sfp1 function and signaling in these cells, resulting in impaired Tra1/SAGA function. Sfp1 is known for its ability to acquire a prion form termed [ISP + ] . At the same time, polyQ toxicity requires certain prions such as [ RNQ + ] and polyQ expansions both stimulate formation and interact with prions .…”

Section: Discussionmentioning

confidence: 99%

“…Sfp1 is known for its ability to acquire a prion form termed [ISP + ]. [97][98][99] At the same time, polyQ toxicity requires certain prions such as [RNQ + ] 52,100,101 and polyQ expansions both stimulate formation and interact with prions. [102][103][104] Thus, one could postulate that recruitment of Sfp1 and/or its prion form [ISP + ] could restrict Tra1 function.…”

Section: Sfp1/torc1 Regulates Tra1 Expression In the Presence Of Toxi...mentioning

confidence: 99%

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Sfp1 links TORC1 and cell growth regulation to the yeast SAGA‐complex component Tra1 in response to polyQ proteotoxicity

Jiang

Berg

Genereaux

et al. 2019

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Chromatin remodeling regulates gene expression in response to the accumulation of misfolded polyQ proteins associated with Huntington's disease (HD). Tra1 is an essential component of both the SAGA/SLIK and NuA4 transcription co‐activator complexes and is linked to multiple cellular processes, including protein trafficking and signaling pathways associated with misfolded protein stress. Cells with compromised Tra1 activity display phenotypes distinct from deletions encoding components of the SAGA and NuA4 complexes, indicating a potentially unique regulatory role of Tra1 in the cellular response to protein misfolding. Here, we employed a yeast model to define how the expression of toxic polyQ expansion proteins affects Tra1 expression and function. Expression of expanded polyQ proteins mimics deletion of SAGA/NuA4 components and results in growth defects under stress conditions. Moreover, deleting genes encoding SAGA and, to a lesser extent, NuA4 components exacerbates polyQ toxicity. Also, cells carrying a mutant Tra1 allele displayed increased sensitivity to polyQ toxicity. Interestingly, expression of polyQ proteins upregulated the expression of TRA1 and other genes encoding SAGA components, revealing a feedback mechanism aimed at maintaining Tra1 and SAGA functional integrity. Moreover, deleting the TORC1 (Target of Rapamycin) effector SFP1 abolished upregulation of TRA1 upon expression of polyQ proteins. While Sfp1 is known to adjust ribosome biogenesis and cell size in response to stress, we identified a new role for Sfp1 in the control of TRA1 expression, linking TORC1 and cell growth regulation to the SAGA acetyltransferase complex during misfolded protein stress.

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Section: Discussionmentioning

confidence: 99%

Section: Sfp1/torc1 Regulates Tra1 Expression In the Presence Of Toxi...mentioning

confidence: 99%

Sfp1 links TORC1 and cell growth regulation to the yeast SAGA‐complex component Tra1 in response to polyQ proteotoxicity

Jiang

Berg

Genereaux

et al. 2019

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“…All the plasmids mentioned in this work are derivatives of centromeric pRS315 ( LEU2 ) or pRS316 ( URA3 ) vectors [ 23 ]. U-1A-D1628 [ 24 ] and U-14-D1690 are 1A-D1628 derivatives containing pRS316-SUP45 [ 11 ] and pRSU1 [ 25 ] plasmids, as a source of the essential SUP45 or SUP35 genes, respectively. The U-14-D1690 strain was obtained as follows: first, a Leu + Ura − haploid segregant (14-D1690) was sporulated from diploid obtained via cross between U-1A-D1628 and L-12-D1682 [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…The U-14-D1690 strain was obtained as follows: first, a Leu + Ura − haploid segregant (14-D1690) was sporulated from diploid obtained via cross between U-1A-D1628 and L-12-D1682 [ 26 ]. Then the pRSU1 plasmid was substituted for the pRSU2 [ 25 ] by selecting Leu − Ura + strain among 14-D1690 [pRSU2] transformants. Yeast strains were cultivated at 26 °C in standard solid and liquid media: YEPD (rich media) and SC (synthetic media).…”

Section: Methodsmentioning

confidence: 99%

Gene Amplification as a Mechanism of Yeast Adaptation to Nonsense Mutations in Release Factor Genes

Maksiutenko

Barbitoff

Matveenko

et al. 2021

Genes

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Protein synthesis (translation) is one of the fundamental processes occurring in the cells of living organisms. Translation can be divided into three key steps: initiation, elongation, and termination. In the yeast Saccharomyces cerevisiae, there are two translation termination factors, eRF1 and eRF3. These factors are encoded by the SUP45 and SUP35 genes, which are essential; deletion of any of them leads to the death of yeast cells. However, viable strains with nonsense mutations in both the SUP35 and SUP45 genes were previously obtained in several groups. The survival of such mutants clearly involves feedback control of premature stop codon readthrough; however, the exact molecular basis of such feedback control remain unclear. To investigate the genetic factors supporting the viability of these SUP35 and SUP45 nonsense mutants, we performed whole-genome sequencing of strains carrying mutant sup35-n and sup45-n alleles; while no common SNPs or indels were found in these genomes, we discovered a systematic increase in the copy number of the plasmids carrying mutant sup35-n and sup45-n alleles. We used the qPCR method which confirmed the differences in the relative number of SUP35 and SUP45 gene copies between strains carrying wild-type or mutant alleles of SUP35 and SUP45 genes. Moreover, we compare the number of copies of the SUP35 and SUP45 genes in strains carrying different nonsense mutant variants of these genes as a single chromosomal copy. qPCR results indicate that the number of mutant gene copies is increased compared to the wild-type control. In case of several sup45-n alleles, this was due to a disomy of the entire chromosome II, while for the sup35-218 mutation we observed a local duplication of a segment of chromosome IV containing the SUP35 gene. Taken together, our results indicate that gene amplification is a common mechanism of adaptation to nonsense mutations in release factor genes in yeast.

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“…45 [ISP+], so named because its phenotype is the reverse of that of [PSI+], antisuppression (decreased read-through of premature termination codons), is a prion of Sfp1p. 46,47 Sfp1p is a transcription factor that promotes transcription of ribosomal protein genes and ribosome biogenesis genes. 48 The [ISP+] prion, unlike sf p1Δ, produces an increased level of transcription of the SUP35 gene, indicating a unique action of the prion and explaining the antisuppressor phenotype.…”

Section: ■ Spectrum Of Yeast and Fungal Prionsmentioning

confidence: 99%

Amyloids and Yeast Prion Biology

et al. 2013

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The prions (infectious proteins) of Saccharomyces cerevisiae are proteins acting as genes, by templating their conformation from one molecule to another in analogy to DNA templating its sequence. Most yeast prions are amyloid forms of normally soluble proteins, and a single protein sequence can have any of several self-propagating forms (called prion strains or variants), analogous to the different possible alleles of a DNA gene. A central issue in prion biology is the structural basis of this conformational templating process. The in-register parallel β sheet structure found for several infectious yeast prion amyloids naturally suggests an explanation for this conformational templating. While most prions are plainly diseases, the [Het-s] prion of Podospora anserina may be a functional amyloid, with important structural implications. Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.

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Novel Non-Mendelian Determinant Involved in the Control of Translation Accuracy in Saccharomyces cerevisiae

Cited by 85 publications

References 51 publications

Sfp1 links TORC1 and cell growth regulation to the yeast SAGA‐complex component Tra1 in response to polyQ proteotoxicity

Sfp1 links TORC1 and cell growth regulation to the yeast SAGA‐complex component Tra1 in response to polyQ proteotoxicity

Gene Amplification as a Mechanism of Yeast Adaptation to Nonsense Mutations in Release Factor Genes

Amyloids and Yeast Prion Biology

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