Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate

Francesca Rapino (), Zhaoli Zhou, Ana Maria Roncero Sanchez, Marc Joiret, Christian Seca, Najla El Hachem, Gianluca Valenti, Sara Latini, Kateryna Shostak, Liesbet Geris, Ping Li, Gang Huang, Gabriel Mazzucchelli, Dominique Baiwir, Christophe J. Desmet, Alain Chariot, Michel Georges and Pierre Close ()
Additional contact information
Francesca Rapino: University of Liège
Zhaoli Zhou: University of Liège
Ana Maria Roncero Sanchez: University of Liège
Marc Joiret: University of Liège
Christian Seca: University of Liège
Najla El Hachem: University of Liège
Gianluca Valenti: University of Liège
Sara Latini: University of Liège
Kateryna Shostak: University of Liège
Liesbet Geris: University of Liège
Ping Li: Shanghai University of Medicine and Health Sciences
Gang Huang: Shanghai University of Medicine and Health Sciences
Gabriel Mazzucchelli: University of Liège
Dominique Baiwir: University of Liège
Christophe J. Desmet: University of Liège
Alain Chariot: University of Liège
Michel Georges: University of Liège
Pierre Close: University of Liège

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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 mcm5s2 wobble uridine tRNA modification (U34-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U34-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 U34-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22254-5

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DOI: 10.1038/s41467-021-22254-5

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