生物
核糖体
泛素连接酶
泛素
细胞生物学
核糖体蛋白
翻译(生物学)
蛋白质稳态
核糖体RNA
核糖体分析
遗传学
信使核糖核酸
基因
核糖核酸
作者
Keely Oltion,Jordan D Carelli,Tangpo Yang,Stephanie K. See,Hao‐Yuan Wang,Martin Kampmann,Jack Taunton
出处
期刊:Cell
[Elsevier]
日期:2023-01-01
卷期号:186 (2): 346-362.e17
被引量:20
标识
DOI:10.1016/j.cell.2022.12.025
摘要
Ribosomes frequently stall during mRNA translation, resulting in the context-dependent activation of quality control pathways to maintain proteostasis. However, surveillance mechanisms that specifically respond to stalled ribosomes with an occluded A site have not been identified. We discovered that the elongation factor-1α (eEF1A) inhibitor, ternatin-4, triggers the ubiquitination and degradation of eEF1A on stalled ribosomes. Using a chemical genetic approach, we unveiled a signaling network comprising two E3 ligases, RNF14 and RNF25, which are required for eEF1A degradation. Quantitative proteomics revealed the RNF14 and RNF25-dependent ubiquitination of eEF1A and a discrete set of ribosomal proteins. The ribosome collision sensor GCN1 plays an essential role by engaging RNF14, which directly ubiquitinates eEF1A. The site-specific, RNF25-dependent ubiquitination of the ribosomal protein RPS27A/eS31 provides a second essential signaling input. Our findings illuminate a ubiquitin signaling network that monitors the ribosomal A site and promotes the degradation of stalled translation factors, including eEF1A and the termination factor eRF1.
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