Chromate-induced sulfur starvation and mRNA mistranslation in yeast are linked in a common mechanism of Cr toxicity.
Toxicity of the environmental carcinogen chromate is known to involve sulfur starvation and also error-prone mRNA translation. Here we reconcile those facts using the yeast model. We demonstrate that: (i) cysteine and methionine starvation mimic Cr-induced translation errors, (ii) genetic suppression of S starvation suppresses Cr-induced mistranslation, and (iii) mistranslation requires cysteine and methionine biosynthesis. Therefore, Cr-induced S starvation is the cause of mRNA mistranslation. This establishes a single, novel pathway mediating the toxicity of chromate.
Holland
Sara L
SL
School of Biology, Institute of Genetics, University of Nottingham, University Park, Nottingham, UK.
Ghosh
Ekalabya
E
Avery
Simon V
SV
D017608:Chromium Compounds / Q000633:toxicity*; D003545:Cysteine / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007202:Indicators and Reagents / Q000633:toxicity*; D008715:Methionine / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D017608:Chromium Compounds; D004268:DNA-Binding Proteins; D007202:Indicators and Reagents; C106765:Met32 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013455:Sulfur; C028801:chromium trioxide; D008715:Methionine; D003545:Cysteine