TRNA TKUUU, TQUUG, and TEUUC Wobble Position Modifications Fine-tune Protein Translation by Promoting Ribosome A-site Binding

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Jul 10

PMID 23836657

Citations 99

Authors

Vanessa Anissa Nathalie Rezgui

Kshitiz Tyagi

Namit Ranjan

Andrey L Konevega

Joerg Mittelstaet

Marina V Rodnina

Matthias Peter

Patrick G A Pedrioli

Affiliations

Soon will be listed here.

Abstract

tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic (tK(UUU)), (tQ(UUG)), and (tE(UUC)). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tK(UUU) to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.

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