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Queuosine‐modified tRNAs confer nutritional control of protein translation
Author(s) -
Tuorto Francesca,
Legrand Carine,
Cirzi Cansu,
Federico Giuseppina,
Liebers Reinhard,
Müller Martin,
EhrenhoferMurray Ann E,
Dittmar Gunnar,
Gröne HermannJosef,
Lyko Frank
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899777
Subject(s) - biology , translation (biology) , transfer rna , computational biology , genetics , protein biosynthesis , bioinformatics , rna , gene , messenger rna
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.