Nascent peptide-induced translation discontinuation in eukaryotes impacts biased amino acid usage in proteomes.
Nascent peptide-induced translation discontinuation in eukaryotes impacts biased amino acid usage in proteomes.
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DOI：
10.1038/s41467-022-35156-x
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发表时间：
2022-12-02
影响因子：
16.6
通讯作者：
Taguchi, Hideki
中科院分区：
文献类型：
--
作者：
Ito, Yosuke;Chadani, Yuhei;Niwa, Tatsuya;Yamakawa, Ayako;Machida, Kodai;Imataka, Hiroaki;Taguchi, Hideki
任何给定的氨基酸序列都需要强健的翻译延伸来塑造蛋白质组。然而，新生多肽有时会破坏核糖体的稳定，因为细菌新生链中连续的负电荷残基可以随机地导致翻译的中断，这种现象被称为内在核糖体不稳定(IRD)。在这里，我们使用发芽酵母和基于人类因素的重组翻译系统，证明IRD也存在于真核翻译中。N-末端富含天冬氨酸(D)或谷氨酸(E)的新生链会改变典型的核糖体动力学，随机中止翻译。虽然真核细胞的核糖体更健壮，可以确保不间断的翻译，但在缺乏肽-tRNA水解酶的细胞中，我们在N末端发现了许多内源性的D/E富含多肽-tRNA，这表明富含D/E的N末端序列的翻译存在固有的失败风险。事实上，生物信息学分析表明，ORF的N-末端区域缺乏D/E富集区，这意味着翻译缺陷部分限制了蛋白质组中氨基酸的总体使用。在这里，作者发现富含酸性氨基酸的新生链会破坏翻译核糖体的稳定性，最终导致真核生物如细菌的随机提前终止。这种提前终止的风险会影响蛋白质组中的氨基酸分布。
Robust translation elongation of any given amino acid sequence is required to shape proteomes. Nevertheless, nascent peptides occasionally destabilize ribosomes, since consecutive negatively charged residues in bacterial nascent chains can stochastically induce discontinuation of translation, in a phenomenon termed intrinsic ribosome destabilization (IRD). Here, using budding yeast and a human factor-based reconstituted translation system, we show that IRD also occurs in eukaryotic translation. Nascent chains enriched in aspartic acid (D) or glutamic acid (E) in their N-terminal regions alter canonical ribosome dynamics, stochastically aborting translation. Although eukaryotic ribosomes are more robust to ensure uninterrupted translation, we find many endogenous D/E-rich peptidyl-tRNAs in the N-terminal regions in cells lacking a peptidyl-tRNA hydrolase, indicating that the translation of the N-terminal D/E-rich sequences poses an inherent risk of failure. Indeed, a bioinformatics analysis reveals that the N-terminal regions of ORFs lack D/E enrichment, implying that the translation defect partly restricts the overall amino acid usage in proteomes. Here the authors find that nascent chains enriched in acidic amino acids destabilize the translating ribosome, eventually leading to stochastic premature termination in eukaryotes as in bacteria. Such risk of premature termination influences the amino acid distribution in the proteomes.
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