Queuosine-modified tRNAs confer nutritional control of protein translation

Francesca Tuorto*, Carine Legrand, Cansu Cirzi, Giuseppina Federico, Reinhard Liebers, Martin Müller, Ann E. Ehrenhofer-Murray, Gunnar Dittmar, Hermann Josef Gröne, Frank Lyko

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    110 Citations (Scopus)

    Abstract

    Global protein translation as well as translation at the codon level can be regulated by tRNA modifications. In eukaryotes, levels of tRNA queuosinylation reflect the bioavailability of the precursor queuine, which is salvaged from the diet and gut microbiota. We show here that nutritionally determined Q-tRNA levels promote Dnmt2-mediated methylation of tRNA Asp and control translational speed of Q-decoded codons as well as at near-cognate codons. Deregulation of translation upon queuine depletion results in unfolded proteins that trigger endoplasmic reticulum stress and activation of the unfolded protein response, both in cultured human cell lines and in germ-free mice fed with a queuosine-deficient diet. Taken together, our findings comprehensively resolve the role of this anticodon tRNA modification in the context of native protein translation and describe a novel mechanism that links nutritionally determined modification levels to effective polypeptide synthesis and cellular homeostasis.

    Original languageEnglish
    Article numbere99777
    JournalEMBO Journal
    Volume37
    Issue number18
    DOIs
    Publication statusPublished - 14 Sept 2018

    Keywords

    • cytosine-5 methylation
    • protein translation
    • queuosine
    • tRNA modifications
    • unfolded protein response

    Fingerprint

    Dive into the research topics of 'Queuosine-modified tRNAs confer nutritional control of protein translation'. Together they form a unique fingerprint.

    Cite this