Ribosomes that stall inappropriately during protein synthesis harbor proteotoxic components linked to cellular stress and neurodegenerative diseases. Molecular mechanisms that rescue stalled ribosomes must selectively detect rare aberrant translational complexes and process the heterogeneous components. Ribosome-associated quality control pathways eliminate problematic messenger RNAs and nascent proteins on stalled translational complexes. In addition, recent studies have uncovered general principles of stall recognition upstream of quality control pathways and fail-safe mechanisms that ensure nascent proteome integrity. Here, we discuss developments in our mechanistic understanding of the detection and rescue of stalled ribosomal complexes in eukaryotes.

在蛋白质合成过程中不适当停止的核糖体含有与细胞应激和神经退行性疾病相关的蛋白质毒性成分。拯救停滞的核糖体的分子机制必须选择性地检测罕见的异常翻译复合物并处理异质成分。核糖体相关的质量控制途径消除了停滞的翻译复合物中有问题的信使 RNA 和新生蛋白质。此外，最近的研究揭示了质量控制途径上游失速识别的一般原则和确保新生蛋白质组完整性的故障安全机制。在这里，我们讨论了我们对真核生物中停滞的核糖体复合物的检测和拯救的机制理解的进展。