Nonsense-mediated decay mutants do not affect programmed −1 frameshifting

Bidou, Laure; Stahl, Guillaume; Hatin, Isabelle; Namy, Olivier; Rousset, Jean‐Pierre; Farabaugh, Philip J.

doi:10.1017/s1355838200000443

Cited by 75 publications

(90 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2), readthrough efficiencies of the three stop codons ranged between 13 and 25% for UAG, 8 and 11% for UGA and 5.5 and 7% for UAA, although the frameshift efficiencies ranged between 22 and 44%. These values are in good agreement with those obtained with other yeast strains (42) as well as with another system depending on a lacZ reporter for Ty1 frameshifting (43). The recorded efficiencies were not significantly different when wild-type strains are compared with their corresponding tRNA modification defective mutants (indicated in white in Fig.…”

Section: Resultssupporting

confidence: 90%

“…This sequence contains a UAG termination codon embedded in a very peculiar nucleotide context and promotes a high level of spontaneous termination readthrough in yeast (36,41). When the UAG stop codon is replaced by UAA or UGA, high readthrough efficiencies were also obtained (42). The second system is based on the slippery sequence of the Ty1 retrotransposon, consisting of the heptanucleotide CUU AGG C, where AGG is a poorly recognized arginine codon.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lecointe¹,

Namy²,

Hatin³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Many different modified nucleotides are found in naturally occurring tRNA, especially in the anticodon region. Their importance for the efficiency of the translational process begins to be well documented. Here we have analyzed the in vivo effect of deleting genes coding for yeast tRNA-modifying enzymes, namely Pus1p, Pus3p, Pus4p, or Trm4p, on termination readthrough and ؉1 frameshift events. To this end, we have transformed each of the yeast deletion strains with a lacZ-luc dual-reporter vector harboring selected programmed recoding sites. We have found that only deletion of the PUS3 gene, encoding the enzyme that introduces pseudouridines at position 38 or 39 in tRNA, has an effect on the efficiency of the translation process. In this mutant, we have observed a reduced readthrough efficiency of each stop codon by natural nonsense suppressor tRNAs. This effect is solely due to the absence of pseudouridine 38 or 39 in tRNA because the inactive mutant protein Pus3[D151A]p did not restore the level of natural readthrough. Our results also show that absence of pseudouridine 39 in the slippery tRNA UAG Leu reduces ؉1 frameshift efficiency. Therefore, the presence of pseudouridine 38 or 39 in the tRNA anticodon arm enhances misreading of certain codons by natural nonsense tRNAs as well as promotes frameshifting on slippery sequences in yeast.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lecointe¹,

Namy²,

Hatin³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The prion state is epigenetically inherited, with rare switching events between the prion and nonprion states (Wickner et al 1995). When the prion appears, Sup35 is depleted due to its incorporation into [PSI 1 ] aggregates, and so the extent of readthrough translation increases from a baseline of 5-10% to 30-40% (Bidou et al 2000). In this way, the yeast prion [PSI 1 ] reveals cryptic genetic variation beyond stop codons by impairing translation termination (True and Lindquist 2000;True et al 2004;Wilson et al 2005).…”

Section: Resultsmentioning

confidence: 99%

Cryptic Genetic Variation Is Enriched for Potential Adaptations

2006

View full text Add to dashboard Cite

Cryptic genetic variation accumulates under weakened selection and has been proposed as a source of evolutionary innovations. Weakened selection may, however, also lead to the accumulation of strongly deleterious or lethal alleles, swamping the effect of any potentially adaptive alleles when they are revealed. Here I model variation that is partially shielded from selection, assuming that unconditionally deleterious variation is more strongly deleterious than variation that is potentially adaptive in a future environment. I find that cryptic genetic variation can be substantially enriched for potential adaptations under a broad range of realistic parameter values, including those applicable to alternative splices and readthrough products generated by the yeast prion [PSI 1 ]. This enrichment is dramatically stronger when multiple simultaneous changes are required to generate a potentially adaptive phenotype. Cryptic genetic variation is likely to be an effective source of useful adaptations at a time of environmental change, relative to an equivalent source of variation that has not spent time in a hidden state.

show abstract

“…One major effect is to specifically stabilize such mRNAs (29). Upf1p may also specifically alter translation termination or translation initiation on these mRNAs (24,(30)(31)(32)(33). The net effect of upf1⌬ is a suppression of the phenotype of premature stop codons.…”

Section: [Psi ؉ ] and Premature Stop Codonsmentioning

confidence: 99%

Genetic interactions between [ PSI ⁺ ] and nonstop mRNA decay affect phenotypic variation

Wilson

Meaux

Parker

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The functions of the eRF3 protein in translation termination and prion propagation are easily separated. The N-terminal domain of eRF3 is required for prion propagation (7,8). Point mutations in, or deletion of, the N-terminal domain disrupt the prion propagation function of yeast eRF3, and the N-terminal domain by itself is sufficient for prion propagation (3,7,9). The translation termination function of eRF3 requires the well conserved C-terminal domain. Deletion of the C-terminal domain is lethal, presumably because of defects in translation termination, and point mutations in the C-terminal domain reduce translation termination efficiency (9). Thus, the prion property of eRF3 is a property of the N-terminal domain, whereas the C-terminal domain is required for translation termination.The ability of eRF3 to exist in [PSI ϩ ] and [psi Ϫ ] states has been conserved during evolution and is present in the eRF3 proteins of several species and genera of yeast (10)(11)(12)(13)(14) ] induces phenotypic variation by suppressing premature stop codons, it has been reported that in seven cases the effect of [PSI ϩ ] was similar to the effect of upf1⌬, which also suppresses premature stop codons (see below) (16). However, it was also reported that in four other cases the effect of [PSI ϩ ] was not mimicked by upf1⌬, suggesting that there may be additional mechanisms by which [PSI ϩ ] affects phenotypes (16).Two lines of evidence suggest that [PSI ϩ ] affects translation termination not only at premature stop codons, but also at wild-type stop codons naturally found at the 3Ј end of coding regions. First, the frequency of extra stop codons just 3Ј of the normal stop codon of yeast genes is higher than expected, suggesting that read-through of the normal stop codons occurs at a frequency that is a significant factor over evolutionary time (19). Second, Namy et al. (20) identified eight genes that had a poor stop codon context. In an artificial reporter gene, translation termination at these stop codon contexts was affected by [PSI ϩ ]. Thus, [PSI ϩ ] might affect phenotypic variation by promoting read-through of normal stop codons (16)(17)(18)20).In addition to PSI directly affecting translation termination of premature and͞or normal stop codons, there may be indirect effects on mRNA stability because translation termination and mRNA stability are intimately linked (16). Two aspects of this link are nonsense-mediated mRNA decay and nonstop mRNA decay. Nonsense-mediated mRNA decay is the process of rapidly degrading mRNAs that contain a premature stop codon (reviewed in ref. 21). It is thought that nonsense-containing mRNAs are recognized as a consequence of premature translation termination. Because [PSI ϩ ] affects the efficiency of translation termination, it may also affect nonsense-mediated mRNA decay. Nonstop mRNA decay is the process of degrading mRNAs that do not contain stop codons (22,23). Nonstop mRNAs are

show abstract

Nonsense-mediated decay mutants do not affect programmed −1 frameshifting

Cited by 75 publications

References 30 publications

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Cryptic Genetic Variation Is Enriched for Potential Adaptations

Genetic interactions between [ PSI ⁺ ] and nonstop mRNA decay affect phenotypic variation

Contact Info

Product

Resources

About

Nonsense-mediated decay mutants do not affect programmed −1 frameshifting

Cited by 75 publications

References 30 publications

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Cryptic Genetic Variation Is Enriched for Potential Adaptations

Genetic interactions between [ PSI + ] and nonstop mRNA decay affect phenotypic variation

Contact Info

Product

Resources

About

Genetic interactions between [ PSI ⁺ ] and nonstop mRNA decay affect phenotypic variation