Journal article
Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast



Publication Details
Authors:
Schaffrath, R.
Publisher:
MDPI
Publication year:
2020
Journal:
BIOMOLECULES
Pages range:
322
Volume number:
10
Issue number:
2
Number of pages:
24
ISSN:
2218-273X

Abstract
Modifications found in the Anticodon Stem Loop (ASL) of tRNAs play important roles in regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t(6)A37) and 5-methoxycarbonyl methyl-2-thiouridine (mcm(5)s(2)U34) are critical ASL modifications that have been linked to several human diseases. The model yeast Saccharomyces cerevisiae is viable despite the absence of both modifications, growth is however greatly impaired. The major observed consequence is a subsequent increase in protein aggregates and aberrant morphology. Proteomic analysis of the t(6)A-deficient strain (sua5 mutant) revealed a global mistranslation leading to protein aggregation without regard to physicochemical properties or t(6)A-dependent or biased codon usage in parent genes. However, loss of sua5 led to increased expression of soluble proteins for mitochondrial function, protein quality processing/trafficking, oxidative stress response, and energy homeostasis. These results point to a global function for t(6)A in protein homeostasis very similar to mcm(5)/s(2)U modifications.


Keywords
Protein aggregation, tRNA modification

Last updated on 2021-19-01 at 15:34