TRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding

Vanessa Anissa Nathalie Rezgui, Kshitiz Tyagi, Namit Ranjan, Audrey L. Konevega, Joerg Mittelstaet, Marina V. Rodnina, Matthias Peter, P.G.A. Pedrioli

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    91 Citations (Scopus)

    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 tRNAUUU Lys (tK), tRNAUUG Gln (tQ), and tRNAUUC Glu (tE). 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 to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.
    Original languageEnglish
    Pages (from-to)12289-12294
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume110
    Issue number30
    DOIs
    Publication statusPublished - 23 Jul 2013

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