Journal
PLOS GENETICS
Volume 11, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1005706
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Funding
- US National Science Foundation [CHE-1308839]
- US National Institute of Environmental Health Science [ES002109, ES017010]
- Singapore-MIT Alliance for Research and Technology, National Research Foundation of Singapore
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1308839] Funding Source: National Science Foundation
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Post-transcriptional modifications of transfer RNAs (tRNAs) have long been recognized to play crucial roles in regulating the rate and fidelity of translation. However, the extent to which they determine global protein production remains poorly understood. Here we use quantitative proteomics to show a direct link between wobble uridine 5-methoxycarbonylmethyl (mcm5) and 5-methoxy-carbonyl-methyl-2-thio (mcm(5)s(2)) modifications catalyzed by tRNA methyltransferase 9 (Trm9) in tRNA(Arg(UCU)) and tRNA(Glu(UUC)) and selective translation of proteins from genes enriched with their cognate codons. Controlling for bias in protein expression and alternations in mRNA expression, we find that loss of Trm9 selectively impairs expression of proteins from genes enriched with AGA and GAA codons under both normal and stress conditions. Moreover, we show that AGA and GAA codons occur with high frequency in clusters along the transcripts, which may play a role in modulating translation. Consistent with these results, proteins subject to enhanced ribosome pausing in yeast lacking mcm(5)U and mcm(5)s(2)U are more likely to be down-regulated and contain a larger number of AGA/GAA clusters. Together, these results suggest that Trm9-catalyzed tRNA modifications play a significant role in regulating protein expression within the cell.
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