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Title

Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation

Authors

Thomas J. Begley, University at Albany, State University of New York
Wenjun Deng, Massachusetts Institute of Technology
I. Ramesh Babu, Massachusetts Institute of Technology
Dan Su, Massachusetts Institute of Technology
Shanye Yin, Massachusetts Institute of Technology
Peter C. Dedon, Massachusetts Institute of Technology

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Document Type

Article

Publication Date

12-15-2015

DOI

https://doi.org/10.1371/journal.pgen.1005706

Abstract

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 (mcm⁵s²) 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 mcm⁵U and mcm⁵s²U 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.

Comments

This is the Publisher’s PDF of the following article made available by PLoS Genetics: Deng W, Babu IR, Su D, Yin S, Begley TJ, et al. (2015) Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation. PLOS Genetics 11(12): e1005706. https://doi.org/10.1371/journal.pgen.1005706

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Begley, Thomas J.; Deng, Wenjun; Babu, I. Ramesh; Su, Dan; Yin, Shanye; and Dedon, Peter C., "Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation" (2015). Biological Sciences Faculty Scholarship. 29.
https://scholarsarchive.library.albany.edu/biology_fac_scholar/29