期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22254-5
关键词
-
资金
- Incentive Grant for Scientific Research from the FNRS [MIS F:4532.13]
- Concerted Research Action Program (tRAME)
- Belgian Foundation against Cancer [F/2016/840, F/2019/097]
- Walloon Excellence in Life Sciences and Biotechnology (WELBIO)
- National Natural Science Foundation of China (NSFC) [81803581]
- Shanghai Institutions of Higher Learning2018 [TP2018080, JZ2018005]
- Foundation Leon Fredericq
- University of Liege [FSR: C-15/44]
Wobble uridine (U-34) tRNA modifications are important for decoding AA-ending codons. The U-34-codon content of mRNAs can predict changes in ribosome translation elongation, while the resulting outcome in protein expression relies on specific hydrophilic motifs-dependent protein aggregation and clearance.
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. Wobble uridine (U-34) tRNA modifications are important for the decoding of AA-ending codons. Here the authors show that while the U-34-codon content of mRNAs are predictive of changes in ribosome translation elongation, the resulting outcome in protein expression also relies on specific hydrophilic motifs-dependent protein aggregation and clearance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据