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Open AccessArticle

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

1
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32603, USA
2
Institut für Biologie, Fachgebiet Mikrobiologie, Universität Kassel, 34132 Kassel, Germany
3
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
4
The RNA Institute, College of Arts and Science, University at Albany, SUNY, Albany, NY 12222, USA
5
University of Florida Genetics Institute, Gainesville, FL 32608, USA
*
Author to whom correspondence should be addressed.
Contributed equally.
Present address, Institute for Biochemistry and Molecular Biology, Stefan-Meier-Straße 17, 79104 Freiburg, Germany.
Biomolecules 2020, 10(2), 322; https://doi.org/10.3390/biom10020322
Received: 15 January 2020 / Revised: 10 February 2020 / Accepted: 11 February 2020 / Published: 18 February 2020
(This article belongs to the Collection RNA Modifications)
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. View Full-Text
Keywords: tRNA modification; protein aggregation tRNA modification; protein aggregation
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Pollo-Oliveira, L.; Klassen, R.; Davis, N.; Ciftci, A.; Bacusmo, J.M.; Martinelli, M.; DeMott, M.S.; Begley, T.J.; Dedon, P.C.; Schaffrath, R.; de Crécy-Lagard, V. Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast. Biomolecules 2020, 10, 322.

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