Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate
17 мая 2021 года
04:45
Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate
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Title: Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate
Author, co-author: Rapino, Francesca; RONCERO SANCHEZ, Ana Maria; ZHOU, ZHAOLI; Joiret, Marc; Seca, Christian; El Hachem, Najla; Valenti, Gianluca; latini, sara; Shostak, Kateryna; Geris, Liesbet; Li, Ping; Huang, Gang; Mazzucchelli, Gabriel; Baiwir, Dominique; Desmet, Christophe; CHARIOT, Alain; Georges, Michel; Close, Pierre
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 reg- ulation 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


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Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate
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* These authors have contributed equally to this work.
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[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 reg- ulation 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
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Автоматическая система мониторинга и отбора информации
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