Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 15 January 2020 / Approved: 17 January 2020 / Online: 17 January 2020 (10:20:39 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Biomolecules 2020, 10, 322
DOI: 10.3390/biom10020322

Abstract

regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t6A37) and 5-methoxycarbonylmethyl-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 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.

Subject Areas

tRNA modification; protein aggregation

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