Reference : Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.
Rapino, Francesca* mailto [Université de Liège - ULiège > > GIGA Stem Cells - Cancer Signaling >]
RONCERO SANCHEZ, Ana Maria* [> >]
Joiret, Marc [Université de Liège - ULiège > > GIGA In silico medecine - Biomechanics Research Unit >]
Seca, Christian [Université de Liège - ULiège > > GIGA Stem Cells - Cancer Signaling >]
El Hachem, Najla [Université de Liège - ULiège > > GIGA Stem Cells - Cancer Signaling >]
Valenti, Gianluca [Université de Liège - ULiège > Département de langues et littératures romanes > Langue et littérature italiennes >]
Latini, Sara [> >]
Shostak, Kateryna mailto [Université de Liège - ULiège > Département de pharmacie > Chimie médicale >]
Geris, Liesbet mailto [Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique >]
Li, Ping [> >]
Huang, Gang [> >]
Mazzucchelli, Gabriel [Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.) >]
Baiwir, Dominique [Université de Liège - ULiège > > GIGA Platforms >]
Desmet, Christophe [Université de Liège - ULiège > > GIGA I3 - Cellular and Molecular Immunology >]
Chariot, Alain [Université de Liège - ULiège > > GIGA Stem Cells - Medical Chemistry >]
Georges, Michel mailto [Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale >]
Close, Pierre [Université de Liège - ULiège > > GIGA Stem Cells - Cancer Signaling >]
* These authors have contributed equally to this work.
Nature Communications
Nature Publishing Group
Yes (verified by ORBi)
United Kingdom
[en] Amino Acids/chemistry/genetics/metabolism ; Cell Line, Tumor ; Codon Usage ; Gene Knockdown Techniques ; Humans ; Hydrophobic and Hydrophilic Interactions ; Multienzyme Complexes/genetics/metabolism ; Peptide Chain Elongation, Translational ; Protein Aggregates/genetics ; Proteolysis ; Proteomics ; RNA Processing, Post-Transcriptional ; RNA, Messenger/metabolism ; RNA, Transfer/genetics/metabolism ; Uridine/metabolism
[en] Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm(5)s(2) wobble uridine tRNA modification (U(34)-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U(34)-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U(34)-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis.
GIGA‐Research - GIGA‐R
Fonds de la Recherche Scientifique - F.R.S.-FNRS ; Fondation contre le Cancer ; WELBIO (Belgique) ; Université de Liège - ULiège
Researchers ; Professionals ; Students ; General public ; Others

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