Journal article
Misactivation of multiple starvation responses in yeast by loss of tRNA modifications
Publication Details
Authors: | Bruch, A.; Schaffrath, R.; Klassen, R.; Laguna, T.; Butter, F. |
Publisher: | OXFORD UNIV PRESS |
Publication year: | 2020 |
Journal: | Nucleic Acids Research |
Pages range : | 7307-7320 |
Journal acronym: | NAR |
Volume number: | 48 |
Issue number: | 13 |
Start page: | 7307 |
End page: | 7320 |
Number of pages: | 14 |
ISSN: | 0305-1048 |
eISSN: | 1362-4962 |
DOI-Link der Erstveröffentlichung: |
Abstract
Previously, combined loss of different anticodon loop modifications was shown to impair the function of distinct tRNAs in Saccharomyces cerevisiae. Surprisingly, each scenario resulted in shared cellular phenotypes, the basis of which is unclear. Since loss of tRNA modification may evoke transcriptional responses, we characterized global transcription patterns of modification mutants with defects in either tRNA(UUG)(Gln) or tRNA(UUU)(Lys) function. We observe that the mutants share inappropriate induction of multiple starvation responses in exponential growth phase, including derepression of glucose and nitrogen catabolite-repressed genes. In addition, autophagy is prematurely and inadequately activated in the mutants. We further demonstrate that improper induction of individual starvation genes as well as the propensity of the tRNA modification mutants to form protein aggregates are diminished upon overexpression of tRNA(UUG)(Gln) or tRNA(UUU)(Lys), the tRNA species that lack the modifications of interest. Hence, our data suggest that global alterations in mRNA translation and proteostasis account for the transcriptional stress signatures that are commonly triggered by loss of anticodon modifications in different tRNAs.
Previously, combined loss of different anticodon loop modifications was shown to impair the function of distinct tRNAs in Saccharomyces cerevisiae. Surprisingly, each scenario resulted in shared cellular phenotypes, the basis of which is unclear. Since loss of tRNA modification may evoke transcriptional responses, we characterized global transcription patterns of modification mutants with defects in either tRNA(UUG)(Gln) or tRNA(UUU)(Lys) function. We observe that the mutants share inappropriate induction of multiple starvation responses in exponential growth phase, including derepression of glucose and nitrogen catabolite-repressed genes. In addition, autophagy is prematurely and inadequately activated in the mutants. We further demonstrate that improper induction of individual starvation genes as well as the propensity of the tRNA modification mutants to form protein aggregates are diminished upon overexpression of tRNA(UUG)(Gln) or tRNA(UUU)(Lys), the tRNA species that lack the modifications of interest. Hence, our data suggest that global alterations in mRNA translation and proteostasis account for the transcriptional stress signatures that are commonly triggered by loss of anticodon modifications in different tRNAs.
