A role for ubiquitin in the clearance of nonfunctional rRNAs
A role for ubiquitin in the clearance of nonfunctional rRNAs
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DOI：
10.1101/gad.1775609
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发表时间：
2009-04-15
影响因子：
10.5
通讯作者：
Ohno, Mutsuhito
中科院分区：
文献类型：
--
作者：
Fujii, Kotaro;Kitabatake, Makoto;Ohno, Mutsuhito
质量控制机制在核糖体生物发生的各个步骤中起作用，以确保生产功能性核糖体颗粒。先前有报道称，含有非功能性突变rRNA的成熟核糖体颗粒也被细胞质量控制系统识别并选择性去除（非功能性rRNA衰变[NRD]）。在这里，我们发现25S rRNA的NRD需要泛素E3连接酶组分Rtt101p及其相关蛋白Mms1p，这些蛋白先前被确定为参与DNA修复的因子。我们发现一组与无功能核糖体颗粒相关的蛋白质以依赖rtt101 - mms1的方式泛素化。当修饰的泛素分子过表达抑制泛素化时，25S NRD被破坏，表明泛素在这一途径中起直接作用。这些结果揭示了DNA修复和rrna质量控制之间意想不到的联系。我们的研究结果支持一种模型，即在对DNA和rRNA有害的基因毒性应激过程中，一种常见的泛素连接酶复合物触发了对DNA和rRNA损伤的反应。
Quality control mechanisms operate in various steps of ribosomal biogenesis to ensure the production of functional ribosome particles. It was reported previously that mature ribosome particles containing nonfunctional mutant rRNAs are also recognized and selectively removed by a cellular quality control system (nonfunctional rRNA decay [NRD]). Here, we show that the NRD of 25S rRNA requires a ubiquitin E3 ligase component Rtt101p and its associated protein Mms1p, identified previously as factors involved in DNA repair. We revealed that a group of proteins associated with nonfunctional ribosome particles are ubiquitinated in a Rtt101-Mms1-dependent manner. 25S NRD was disrupted when ubiquitination was inhibited by the overexpression of modified ubiquitin molecules, demonstrating a direct role for ubiquitin in this pathway. These results uncovered an unexpected connection between DNA repair and the quality control of rRNAs. Our findings support a model in which responses to DNA and rRNA damages are triggered by a common ubiquitin ligase complex during genotoxic stress harmful to both molecules.