Journal
BIOMOLECULES
Volume 10, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biom10020322
Keywords
tRNA modification; protein aggregation
Categories
Funding
- National Institutes of Health [R01 GM70641]
- National Institute of Environmental Health Science [P30 ES002109]
- Deutsche Forschungsgemeinschaft (DFG) [SCHA750/15, SCHA750/18, SPP1784, SCHA750/20-2, KL2937/1-2]
- NSF Graduate Research Fellowship
- National Institutes of Health MIT Biotechnology Training Program
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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.
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