Journal
GENES
Volume 9, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/genes9110516
Keywords
tRNA anticodon modifications; unfolded protein response; tunicamycin; yeast; elongator complex; Deg1
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [SCHA750/15, SCHA750/18]
- Priority Program SPP1784 Chemical Biology of Native Nucleic Acid Modifications [SCHA750/20, KL2937/1]
- European Union Cost Action [EPITRAN CA16120]
Ask authors/readers for more resources
Modifications in the anticodon loop of transfer RNAs (tRNAs) have been shown to ensure optimal codon translation rates and prevent protein homeostasis defects that arise in response to translational pausing. Consequently, several yeast mutants lacking important anticodon loop modifications were shown to accumulate protein aggregates. Here we analyze whether this includes the activation of the unfolded protein response (UPR), which is commonly triggered by protein aggregation within the endoplasmic reticulum (ER). We demonstrate that two different aggregation prone tRNA modification mutants (elp6 ncs2; elp3 deg1) lacking combinations of 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U: elp3; elp6; ncs2) and pseudouridine (psi: deg1) reduce, rather than increase, splicing of HAC1 mRNA, an event normally occurring as a precondition of UPR induction. In addition, tunicamycin (TM) induced HAC1 splicing is strongly impaired in the elp3 deg1 mutant. Strikingly, this mutant displays UPR independent resistance against TM, a phenotype we found to be rescued by overexpression of tRNA(Gln)(UUG), the tRNA species usually carrying the mcm(5)s(2)U34 and psi 38 modifications. Our data indicate that proper tRNA anticodon loop modifications promote rather than impair UPR activation and reveal that protein synthesis and homeostasis defects in their absence do not routinely result in UPR induction but may relieve endogenous ER stress.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available