tRNA thiolation links translation to stress responses in Saccharomyces cerevisiae.
Although tRNA modifications have been well catalogued, the precise functions of many modifications and their roles in mediating gene expression are still being elucidated. Whereas tRNA modifications were long assumed to be constitutive, it is now apparent that the modification status of tRNAs changes in response to different environmental conditions. The URM1 pathway is required for thiolation of the cytoplasmic tRNAs tGlu(UUC), tGln(UUG), and tLys(UUU) in Saccharomyces cerevisiae. We demonstrate that URM1 pathway mutants have impaired translation, which results in increased basal activation of the Hsf1-mediated heat shock response; we also find that tRNA thiolation levels in wild-type cells decrease when cells are grown at elevated temperature. We show that defects in tRNA thiolation can be conditionally advantageous, conferring resistance to endoplasmic reticulum stress. URM1 pathway proteins are unstable and hence are more sensitive to changes in the translational capacity of cells, which is decreased in cells experiencing stresses. We propose a model in which a stress-induced decrease in translation results in decreased levels of URM1 pathway components, which results in decreased tRNA thiolation levels, which further serves to decrease translation. This mechanism ensures that tRNA thiolation and translation are tightly coupled and coregulated according to need.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Jadyn R
JR
Damon
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
David
D
Pincus
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 ploegh@wi.mit.edu.
Hidde L
HL
Ploegh
D015152:Blotting, Northern; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D008957:Models, Genetic; D009154:Mutation; D014176:Protein Biosynthesis / Q000235:genetics*; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D012351:RNA, Transfer, Gln / Q000235:genetics / Q000378:metabolism; D012352:RNA, Transfer, Glu / Q000235:genetics / Q000378:metabolism; D012357:RNA, Transfer, Lys / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology
D004268:DNA-Binding Proteins; C067168:HSF1 protein, S cerevisiae; D006360:Heat-Shock Proteins; D012331:RNA, Fungal; D012351:RNA, Transfer, Gln; D012352:RNA, Transfer, Glu; D012357:RNA, Transfer, Lys; D029701:Saccharomyces cerevisiae Proteins; D013438:Sulfhydryl Compounds; D014157:Transcription Factors; C406282:URM1 protein, S cerevisiae; D014415:Tunicamycin; D012343:RNA, Transfer