40S subunit dissociation and proteasome-dependent RNA degradation in nonfunctional 25S rRNA decay
40S subunit dissociation and proteasome-dependent RNA degradation in nonfunctional 25S rRNA decay
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DOI：
10.1038/emboj.2012.85
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发表时间：
2012-05-30
期刊：
影响因子：
11.4
通讯作者：
Ohno, Mutsuhito
中科院分区：
文献类型：
--
作者：
Fujii, Kotaro;Kitabatake, Makoto;Ohno, Mutsuhito
真核细胞具有质量控制系统，其消除具有有害突变的非功能性rRNA（非功能性rRNA衰变，NRD）。我们以前曾报道，25 S NRD需要一个E3泛素连接酶复合物，这是参与核糖体泛素化。然而，非功能性核糖体的降解过程仍然未知。在这里，使用遗传筛选，我们确定了两个泛素结合复合物，Cdc 48-Npl 4-Ufd 1复合物（Cdc 48复合物）和蛋白酶体，作为参与25 S NRD的因子。我们发现，非功能性的60 S亚基解离的40 S亚基在Cdc 48复合物依赖的方式，在它被攻击的蛋白酶体。当我们检查在蛋白酶体耗尽条件下积累的非功能性60 S亚基时，大多数突变体25 S rRNA在单核苷酸分辨率下保留了它们的全长。这表明蛋白酶体是触发rRNA降解的重要因素。我们进一步表明，核糖体泛素化可以刺激单独的蛋白酶体的抑制，这表明泛素蛋白酶体依赖的RNA降解发生在更广泛的情况下，包括在一般的rRNA周转。The EMBO Journal（2012）31，2579-2589. doi：10.1038/daj.2012.85; 2012年4月13日在线发布
Eukaryotic cells have quality control systems that eliminate nonfunctional rRNAs with deleterious mutations (nonfunctional rRNA decay, NRD). We have previously reported that 25S NRD requires an E3 ubiquitin ligase complex, which is involved in ribosomal ubiquitination. However, the degradation process of nonfunctional ribosomes has remained unknown. Here, using genetic screening, we identified two ubiquitin-binding complexes, the Cdc48-Npl4-Ufd1 complex (Cdc48 complex) and the proteasome, as the factors involved in 25S NRD. We show that the nonfunctional 60S subunit is dissociated from the 40S subunit in a Cdc48 complex-dependent manner, before it is attacked by the proteasome. When we examined the non-functional 60S subunits that accumulated under proteasome-depleted conditions, the majority of mutant 25S rRNAs retained their full length at a single-nucleotide resolution. This indicates that the proteasome is an essential factor triggering rRNA degradation. We further showed that ribosomal ubiquitination can be stimulated solely by the suppression of the proteasome, suggesting that ubiquitin-proteasome-dependent RNA degradation occurs in broader situations, including in general rRNA turnover. The EMBO Journal (2012) 31, 2579-2589. doi: 10.1038/emboj.2012.85; Published online 13 April 2012