后生动物的细胞通过激活应激反应途径来对内部和外部应激源做出反应,这些应激反应途径旨在重建细胞的稳态或,如果不能做到这一点,触发程序性细胞死亡。翻译过程中的问题,产生于有缺陷的mRNA,tRNAs,核糖体或蛋白质错误折叠,可以激活应激反应途径以及mRNA监测和核糖体质量控制程序。最近,核糖体碰撞已成为翻译应激的中心信号,并显示出引起不同的应激反应。这里,我们回顾了我们目前关于核糖体碰撞之间复杂的相互联系的知识,应激反应途径和mRNA监测。将碰撞核糖体的感知与新生多肽的降解联系起来的中心因素,E3连接酶ZNF598是停滞的核糖体的解离和通过不停止或不停止衰变降解mRNA。我们测试了ZNF598是否在无义介导的mRNA衰减(NMD)中也起作用,但发现它对于这种翻译终止相关的mRNA监测途径是不必要的。与其他最新数据相结合,认为终止密码子处稳定的核糖体停滞是NMD触发信号。
Cells of metazoans respond to internal and external stressors by activating stress response pathways that aim for re-establishing cellular homoeostasis or, if this cannot be achieved, triggering programmed cell death. Problems during translation, arising from defective mRNAs, tRNAs, ribosomes or protein misfolding, can activate stress response pathways as well as mRNA surveillance and ribosome quality control programs. Recently, ribosome collisions have emerged as a central signal for translational stress and shown to elicit different stress responses. Here, we review our current knowledge about the intricate mutual connections between ribosome collisions, stress response pathways and mRNA surveillance. A central factor connecting the sensing of collided ribosomes with degradation of the nascent polypeptides, dissociation of the stalled ribosomes and degradation of the mRNA by no-go or non-stop decay is the E3-ligase ZNF598. We tested whether ZNF598 also plays a role in nonsense-mediated mRNA decay (NMD) but found that it is dispensable for this translation termination-associated mRNA surveillance pathway, which in combination with other recent data argues against stable ribosome stalling at termination codons being the NMD-triggering signal.