Increased tRNA level in yeast cells with mutant translation termination factors eRF1 and eRF3

Zhouravleva, Galina A.; Moskalenko, Svetlana E.; Chabelskaya, Svetlana; Inge-Vechtomov, Sergey G.

doi:10.1134/s0026893306040170

Cited by 9 publications

(11 citation statements)

References 39 publications

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“…Recently, nonsense mutations in SUP35 and SUP45 were shown to have a general effect on increasing tRNA levels (Zhouravleva et al ., 2006). If the levels of tRNAs, including the zymocin targets, were also increased in mtq2 Δ cells that are unable to methylate Sup45, this would provide an explanation for the zymocin resistance of an mtq2 Δ mutant as it has been shown that excess levels of tRNA Glu suppress zymocin toxicity (Butler et al ., 1994; Lu et al ., 2005; Jablonowski et al ., 2006).…”

Section: Resultsmentioning

confidence: 99%

“…In sum, these results indicate that tRNA species including tRNA Glu and tRNA Lys significantly accumulate in sup45 and mtq2 Δ mutants suggesting that deletion in MTQ2 or mutation of SUP45 may have a general effect on tRNA biogenesis. This is congruent with a recent survey that demonstrated up to twofold increases in eight different tRNA species in the sup45‐n set of mutants (Zhouravleva et al ., 2006) that we demonstrated in this study to suppress zymocin (Fig. S2).…”

Section: Resultsmentioning

confidence: 99%

“…This may operate at the level of SUQ5 expression or at the expression levels of other potential suppressor tRNAs. Consistent with this, Zhouravleva et al . (2006) reported that sup35‐n and sup45‐n cells have higher‐than‐normal levels of tRNAs including tRNA species (tRNA Tyr , tRNA Gln and tRNA Trp ) that upon overexpression have nonsense suppressor activity in yeast (Beier and Grimm, 2001).…”

Section: Discussionmentioning

confidence: 99%

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tRNA and protein methylase complexes mediate zymocin toxicity in yeast

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Jablonowski

et al. 2008

Molecular Microbiology

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SummaryModification of Saccharomyces cerevisiae tRNA anticodons at the wobble uridine (U34) position is required for tRNA cleavage by the zymocin tRNase killer toxin from Kluyveromyces lactis. Hence, U34 modification defects including lack of the U34 tRNA methyltransferase Trm9 protect against tRNA cleavage and zymocin. Using zymocin as a tool, we have identified toxin-resistant mutations in TRM9 that are likely to affect the U34 methylation reaction. Most strikingly, C-terminal truncations in Trm9 abolish interaction with Trm112, a protein shown to individually purify with Lys9 and two more methylases, Trm11 and Mtq2. Downregulation of a GAL1-TRM112 allele protects against zymocin whereas LYS9, TRM11 and MTQ2 are dosage suppressors of zymocin. Based on immune precipitation studies, the latter scenario correlates with competition for Trm112 and in excess, some of these Trm112 partners interfere with formation of the toxin-relevant Trm9·Trm112 complex. In contrast to trm11D or lys9D cells, trm112D and mtq2D null mutants are zymocin resistant. In line with the identified role that methylation of Sup45 by Mtq2 has for translation termination by the release factor dimer Sup45·Sup35, we observe that SUP45 overexpression and sup45 mutants suppress zymocin. Intriguingly, this suppression correlates with upregulated levels of tRNA species targeted by zymocin's tRNase activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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tRNA and protein methylase complexes mediate zymocin toxicity in yeast

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Zink

Jablonowski

et al. 2008

Molecular Microbiology

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“…For example, the total level of all tRNAs under study was 1.5-to 2-fold higher in sup45-105 mutant than in sup45-101 mutant (Zhouravleva et al 2006). This fact allowed us to propose that each sup45-n mutant has its own "optimized level of suppression".…”

Section: Mutant Strain Background Does Not Inxuence the Level Of Readmentioning

confidence: 92%

The paradox of viable sup45 STOP mutations: a necessary equilibrium between translational readthrough, activity and stability of the protein

et al. 2009

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The mechanisms leading to non-lethality of nonsense mutations in essential genes are poorly understood. Here, we focus on the factors influencing viability of yeast cells bearing premature termination codons (PTCs) in the essential gene SUP45 encoding translation termination factor eRF1. Using a dual reporter system we compared readthrough efficiency of the natural termination codon of SUP45 gene, spontaneous sup45-n (nonsense) mutations, nonsense mutations obtained by site-directed mutagenesis (76Q --> TAA, 242R --> TGA, 317L --> TAG). The nonsense mutations in SUP45 gene were shown to be situated in moderate contexts for readthrough efficiency. We showed that readthrough efficiency of some of the mutations present in the sup45 mutants is not correlated with full-length Sup45 protein amount. This resulted from modification of both sup45 mRNA stability which varies 3-fold among sup45-n mutants and degradation rate of mutant Sup45 proteins. Our results demonstrate that some substitutions in the place of PTCs decrease Sup45 stability. The viability of sup45 nonsense mutants is therefore supported by diverse mechanisms that control the final amount of functional Sup45 in cells.

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“…The majority of SUP45 and SUP35 mutations studied lead to the increase in endogenous tRNA level. This can explain the viability of cells with nonsense mutations in SUP45 and SUP35 genes [5].…”

Section: Introductionmentioning

confidence: 99%

Influence of UPF genes on severity of SUP45 mutations

Zhouravleva

Gryzina

2012

Mol Biol

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Eukaryotic cells possess a special mechanism for the degradation of mRNAs containing prema ture termination codons (PTCs), referred to as NMD (nonsense mediated mRNA decay). The strength of this pathway depends on the recognition of the PTCs by translational machinery and the interaction of trans lation termination factors eRF1 and eRF3 with Upf1, Upf2 and Upf3 proteins in Sachromyces cerevisiae yeast. Previously, we have shown that the decrease of eRF1 protein amounts in sup45 nonsense mutants leads to the impairment of NMD. Here we show that the deletion of UPF1 or UPF2 genes leads to an increase in the viability of sup45 mutants, while the effect of UPF3 gene deletion is allele specific. Two hybrid data have shown that amino acid residues 1 555 of Upf1 protein interact with eRF1. Any UPF gene deletion leads to allosupression of the adel1 14 mutation without a change in eRF1 content. The Upf1 depletion does not influence the synthetic lethality of sup45 mutations and the [PSI + ] prion. It is possible that the absence of Upf1 (or its activator Upf2) leads to a more effective formation of the translation termination complex and consequently to the increased viability of the cells containing mutant termination factors.

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Increased tRNA level in yeast cells with mutant translation termination factors eRF1 and eRF3

Cited by 9 publications

References 39 publications

tRNA and protein methylase complexes mediate zymocin toxicity in yeast

tRNA and protein methylase complexes mediate zymocin toxicity in yeast

The paradox of viable sup45 STOP mutations: a necessary equilibrium between translational readthrough, activity and stability of the protein

Influence of UPF genes on severity of SUP45 mutations

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