The ASC-1 Complex Disassembles Collided Ribosomes
The ASC-1 Complex Disassembles Collided Ribosomes
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DOI：
10.1016/j.molcel.2020.06.006
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发表时间：
2020-08-20
期刊：
影响因子：
16
通讯作者：
Hegde, Ramanujan S.
中科院分区：
文献类型：
--
作者：
Juszkiewicz, Szymon;Speldewinde, Shaun H.;Hegde, Ramanujan S.
翻译速度过慢的核糖体会与尾随的核糖体发生碰撞。ZNF 598是一种泛素连接酶，可泛素化核糖体40 S亚基上的位点，启动mRNA和蛋白质质量控制的途径。碰撞的核糖体复合物必须被分解以启动下游质量控制，但分解的机制基础尚不清楚。在这里，我们重建的拆卸碰撞多核糖体在哺乳动物无细胞系统。含有ASCC 3解旋酶的广泛保守的ASC-1复合物（ASCC）在ATP依赖性反应中分解主导核糖体。ZNF 598的40 S泛素化作用是必需的，而不是核糖体结合，而GTP依赖性因子，包括Pelo-Hbs 1 L核糖体拯救复合物则不需要。一旦路障被移除，尾随的核糖体就可以伸长，只有在它们随后停滞并发生碰撞时才能成为目标。这些发现定义了ASCC在核糖体相关质量控制过程中的特定作用，并确定了其活性的分子靶点。
Translating ribosomes that slow excessively incur collisions with trailing ribosomes. Persistent collisions are detected by ZNF598, a ubiquitin ligase that ubiquitinates sites on the ribosomal 40S subunit to initiate pathways of mRNA and protein quality control. The collided ribosome complex must be disassembled to initiate downstream quality control, but the mechanistic basis of disassembly is unclear. Here, we reconstitute the disassembly of a collided polysome in a mammalian cell-free system. The widely conserved ASC-1 complex (ASCC) containing the ASCC3 helicase disassembles the leading ribosome in an ATP-dependent reaction. Disassembly, but not ribosome association, requires 40S ubiquitination by ZNF598, but not GTP-dependent factors, including the Pelo-Hbs1L ribosome rescue complex. Trailing ribosomes can elongate once the roadblock has been removed and only become targets if they subsequently stall and incur collisions. These findings define the specific role of ASCC during ribosome-associated quality control and identify the molecular target of its activity.