Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast
Name
biomolecules-10-00322-v2.pdf
Size
7.51 MB
Format
Adobe PDF
Checksum (MD5)
4acb1552f98ac9af4dd6eba82050cc6a
Author(s)
Pollo-Oliveira, Leticia
Klassen, Roland
Davis, Nick
Ciftci, Akif
Bacusmo, Jo Marie
Martinelli, Maria
DeMott, Michael S.
Begley, Thomas J.
Dedon, Peter C
Schaffrath, Raffael
Date Issued
February 18, 2020
Journal
Biomolecules
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Pollo-Oliveira, Leticia, et al., "Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast." Biomolecules 10, 2 (2020): no. 322 doi 10.3390/biom10020322 ©2020 Author(s)
Version
Final published version
Abstract
Modifications found in the Anticodon Stem Loop (ASL) of tRNAs play important roles in regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t6A37) and 5-methoxycarbonyl methyl-2-thiouridine (mcm5s2U34) 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 t6A-deficient strain (sua5 mutant) revealed a global mistranslation leading to protein aggregation without regard to physicochemical properties or t6A-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 t6A in protein homeostasis very similar to mcm5/s2U modifications. Keywords: tRNA modification; protein aggregation
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3390/biom10020322
