Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover
Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover
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DOI：
10.1016/j.molcel.2022.08.018
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发表时间：
2022-09-15
期刊：
影响因子：
16
通讯作者：
Inada, Toshifumi
中科院分区：
文献类型：
--
作者：
Li, Sihan;Ikeuchi, Ken;Inada, Toshifumi
细胞可以通过感知核糖体碰撞和采用质量控制途径来响应停滞的核糖体。然而，核糖体停滞如何在没有碰撞的情况下解决，仍然是难以捉摸的。在这里，我们将重点放在解码缺陷核糖体所表现出的非碰撞停滞上，将Fap1确定为通过uS3的多聚泛素化触发18S非功能性rRNA衰变的停滞传感器。核糖体分析显示Fap1在翻译起始位点富集，但也与延长单个核糖体有关。Fap1结合的核糖体的冷冻电镜结构阐明了Fap1同时在入口和出口通道探测mRNA，这表明mRNA停滞感测活性，并且Fap1在空间上阻碍了典型碰撞的二核糖体的形成。我们的研究结果表明，单个停滞的核糖体是核糖体功能障碍的潜在信号，导致核糖体本身的加速周转。
Cells can respond to stalled ribosomes by sensing ribosome collisions and employing quality control path-ways. How ribosome stalling is resolved without collisions, however, has remained elusive. Here, focusing on noncolliding stalling exhibited by decoding-defective ribosomes, we identified Fap1 as a stalling sensor trig-gering 18S nonfunctional rRNA decay via polyubiquitination of uS3. Ribosome profiling revealed an enrich-ment of Fap1 at the translation initiation site but also an association with elongating individual ribosomes. Cryo-EM structures of Fap1-bound ribosomes elucidated Fap1 probing the mRNA simultaneously at both the entry and exit channels suggesting an mRNA stasis sensing activity, and Fap1 sterically hinders the formation of canonical collided di-ribosomes. Our findings indicate that individual stalled ribosomes are the potential signal for ribosome dysfunction, leading to accelerated turnover of the ribosome itself.