mRNAs involved in copper homeostasis are regulated by the nonsense-mediated mRNA decay pathway depending on environmental conditions

Peccarelli, Megan; Scott, Taylor D.; Steele, M. E. R.; Kebaara, Bessie W.

doi:10.1016/j.fgb.2015.12.011

Cited by 8 publications

(46 citation statements)

References 38 publications

(87 reference statements)

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“…In agreement with our previous study (Peccarelli et al 2016), we found that in rich media the major COX19 mRNA isoform is directly regulated by NMD, while in the same conditions COX23 is indirectly regulated by the pathway (Fig. 1b, c; Table 2).…”

Section: Resultssupporting

confidence: 93%

“…All yeast strains used were grown under the conditions indicated in the table ND not determined a Half-lives were reported previously (Peccarelli et al 2016)…”

Section: Resultsmentioning

confidence: 99%

“…In addition, regulation of natural mRNAs by NMD can be growth condition specific. These observations have led to the hypothesis that these NMD targeting features can function in specific cellular context and environmental conditions (Peccarelli et al 2016). …”

Section: Introductionmentioning

confidence: 99%

“…The COX19 mRNAs long 3′-UTR contributes to the degradation of the mRNA by NMD. Alternatively, despite having a long 3′-UTR, COX23 mRNA is indirectly regulated by the pathway in rich media (Peccarelli et al 2016). Since these mRNAs have NMD targeting features, the pathway could directly regulate them in select environmental conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Since these mRNAs have NMD targeting features, the pathway could directly regulate them in select environmental conditions. For example, we previously found that MAC1 mRNA was directly regulated by NMD in rich media, but not regulated under low copper conditions, when the Mac1p is required (Peccarelli et al 2016). Thus, we examined whether environmental copper levels affect the NMD-mediated regulation of these three mRNAs.…”

Section: Introductionmentioning

confidence: 99%

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The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs

et al. 2018

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The differential regulation of COX17, COX19 and COX23 mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was investigated. The NMD pathway regulates mRNAs that aberrantly terminate translation. This includes mRNAs harboring premature translation termination codons and natural mRNAs. Most natural mRNAs regulated by NMD encode fully functional proteins involved in various cellular processes. However, the cause and targeting of most of these mRNAs by the pathway is not understood. Analysis of a set of mRNAs involved in copper homeostasis showed that a subset of these mRNAs function in mitochondrial copper homeostasis. Here, we examined the regulation of COX17, COX19 and COX23 mRNAs by NMD. These mRNAs encode homologous mitochondrial proteins involved in metallation of cytochrome c oxidase. We found that COX17, COX19 and COX23 mRNAs are differentially regulated by NMD depending on environmental copper levels. A long 3′-UTR contributes to the direct regulation of COX19 mRNA by the pathway. Alternatively, COX23 mRNA contains a long 3′-UTR, but is indirectly regulated by the pathway under two conditions tested here. Analysis of the functionality of the NMD targeting features in COX23 mRNA showed that the COX23 3′-UTR is sufficient to trigger NMD. The regulation of mRNAs involved in mitochondrial copper metabolism by NMD is physiologically significant because excess copper enhances growth of NMD mutants on a non-fermentable carbon source. These findings suggest that regulation of mRNAs encoding homologous proteins by NMD can be differential depending on environmental copper levels. Furthermore, these findings suggest copper ion homeostatic mechanisms in the mitochondria occur at the mRNA level via the NMD pathway.

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Section: Resultssupporting

confidence: 93%

“…All yeast strains used were grown under the conditions indicated in the table ND not determined a Half-lives were reported previously (Peccarelli et al 2016)…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs

et al. 2018

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Nonsense‐mediated mRNA decay of the ferric and cupric reductase mRNAs FRE1 and FRE2 in Saccharomyces cerevisiae

2019

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The nonsense‐mediated mRNA decay (NMD) pathway regulates mRNAs that aberrantly terminate translation. This includes aberrant mRNAs and functional natural mRNAs. Natural mRNA degradation by NMD is triggered by mRNA features and environmental cues. Saccharomyces cerevisiae encodes multiple proteins with ferric and cupric reductase activity. Here, we examined the regulation by NMD of two mRNAs, FRE1 and FRE2, encoding ferric and cupric reductases in S. cerevisiae. We found that FRE2 mRNAs are regulated by NMD under noninducing conditions and that the FRE2 3′‐UTR contributes to the degradation of the mRNAs by NMD. Conversely, FRE1 mRNAs are not regulated by NMD under comparable conditions. These findings suggest that regulation of functionally related mRNAs by NMD can be differential and conditional.

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Variation of the response to metal ions and nonsense‐mediated mRNA decay across different Saccharomyces cerevisiae genetic backgrounds

Wong

Lam

Pai

et al. 2021

Yeast

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Regulation of mRNA steady‐state levels is important in controlling gene expression particularly in response to environmental stimuli. This allows cells to rapidly respond to environment changes. The highly conserved nonsense‐mediated mRNA decay (NMD) pathway was initially identified as a pathway that degrades aberrant mRNAs. NMD is now recognized as a pathway with additional functions including precisely regulating the expression of select natural mRNAs. Majority of these natural mRNAs encode fully functional proteins. Regulation of natural mRNAs by NMD is activated by NMD targeting features and environmental cues. Here, we show that Saccharomyces cerevisiae strains from three genetic backgrounds respond differentially to NMD depending on the environmental stimuli. We found that wild type and NMD mutant W303a, BY4741, and RM11‐1a yeast strains respond similarly to copper in the environment but respond differentially to toxic cadmium. Furthermore, the PCA1 alleles encoding different mRNAs from W303a and RM11‐1a strains are regulated similarly by NMD in response to the bio‐metal copper but differentially in response to toxic cadmium.

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mRNAs involved in copper homeostasis are regulated by the nonsense-mediated mRNA decay pathway depending on environmental conditions

Cited by 8 publications

References 38 publications

The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs

The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs

Nonsense‐mediated mRNA decay of the ferric and cupric reductase mRNAs FRE1 and FRE2 in Saccharomyces cerevisiae

Variation of the response to metal ions and nonsense‐mediated mRNA decay across different Saccharomyces cerevisiae genetic backgrounds

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