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

Abstract

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.

Nonsense-mediated mRNA decay of metal-binding activator MAC1 is dependent on copper levels and 3′-UTR length in Saccharomyces cerevisiae

“…Furthermore, under elevated copper levels, metallothioneins such as CUP1 and CRS5 , and additional genes involved in adaptation to high copper levels are elevated (Figure 1B). We have reported previously that wild-type and NMD mutant yeast strains tolerate high copper levels with the NMD mutants being more tolerant than the wild-type strains (35).…”

“…Therefore, we would anticipate the MAC1 mRNA would be stabilized in wild-type yeast strains under this specific growth condition when higher levels of copper are required. Our previous analysis of mRNAs encoding proteins involved in various aspects of copper homeostasis, demonstrated that regulation of these mRNAs by NMD could be responsive to fluctuations in environmental copper levels and generates physiological consequences to the yeast cells (17,24).…”

Genome-Scale Screening and Combinatorial Optimization of Gene Overexpression Targets to Improve Cadmium Tolerance in Saccharomyces cerevisiae

“…For example, PCA1 encodes a cadmium efflux transporter. Whereas some natural S. cerevisiae isolates harbor a functional PCA1 gene that confers cadmium resistance, most laboratory S. cerevisiae strains including CEN.PK2-1c used in this study contain a nonfunctional Pca1p due to a G970R missense mutation (Adle et al, 2007;Wei et al, 2014;Wong et al, 2021). Therefore, it is unlikely to identify PCA1 as a positive hit via genome-scale screening using a CEN.PK cDNA-derived overexpression library.…”

Nonsense-mediated mRNA decay and metal ion homeostasis and detoxification in Saccharomyces cerevisiae

“…PCA1 mRNA is also regulated by NMD and involved in the protection of the cell from metal toxicity (Guan et al 2006 ; Wong et al 2021 ) PCA1 is an evolutionarily conserved P 1B -type cation-transporting ATPase that is widely distributed from bacteria to humans (Rad et al 1994 ). PCA1 has been proposed to be involved in copper and iron homeostasis (De Freitas et al 2004 ; Rad et al 1994 ).…”

“…The protein encoded by CAD2 functions in the cadmium efflux system of yeast cells (hereafter referred as PCA1 970G ). The PCA1 allele found in most common lab yeast strains possess a missense mutation in the ATP-binding residue conserved in P 1B -type ATPases [hereafter referred as PCA1 970R ; (Adle et al 2007 ; Wong et al 2021 )]. In humans, a substitution in the ATP7B similar to the one found in PCA1 leads to Wilson's disease.…”