Sas10 controls ribosome biogenesis by stabilizing Mpp10 and delivering the Mpp10-Imp3-Imp4 complex to nucleolus

Sas10 controls ribosome biogenesis by stabilizing Mpp10 and delivering the Mpp10-Imp3-Imp4 complex to nucleolus
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Sas10 通过稳定 Mpp10 并将 Mpp10-Imp3-Imp4 复合物递送至核仁来控制核糖体生物合成

DOI:
10.1093/nar/gkz105
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发表时间:
2019-04-08
影响因子:
14.9
通讯作者:
Peng, Jinrong
Peng, Jinrong
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao, Shuyi;Chen, Yayue;Peng, Jinrong

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Mpp10与Imp3和Imp4形成复合物,作为核糖体小亚基(SSU)过程的核心成分。Mpp10还与核仁蛋白Sas10/Utp3相互作用。然而,目前尚不清楚Mpp10-Imp3-Imp4复合物是如何传递到核仁的,以及Mpp10-Sas10复合物的生物学功能是什么。在这里,我们报道了斑马鱼Mpp10和Sas10是消化器官发育所必需的保守核仁蛋白。Mpp10,而不是Sas10/Utp3,是核核定位的Def-Capn3蛋白降解途径的靶标。Sas10通过屏蔽Mpp10上的capn3识别位点来保护Mpp10免受capn3介导的切割。Def与Sas10相互作用形成Def-Sas10-Mpp10复合物,促进capn3介导的Mpp10裂解。重要的是,我们发现Sas10决定了Mpp10-Imp3-Imp4复合物的核仁定位。综上所述,Sas10不仅在将Mpp10- imp3 - imp4复合物运送到核仁以组装SSU过程中至关重要,而且在器官发生过程中微调核仁中Mpp10的转换。
Mpp10 forms a complex with Imp3 and Imp4 that serves as a core component of the ribosomal small subunit (SSU) processome. Mpp10 also interacts with the nucleolar protein Sas10/Utp3. However, it remains unknown how the Mpp10-Imp3-Imp4 complex is delivered to the nucleolus and what biological function the Mpp10-Sas10 complex plays. Here, we report that the zebrafish Mpp10 and Sas10 are conserved nucleolar proteins essential for the development of the digestive organs. Mpp10, but not Sas10/Utp3, is a target of the nucleolus-localized Def-Capn3 protein degradation pathway. Sas10 protects Mpp10 from Capn3-mediated cleavage by masking the Capn3-recognition site on Mpp10. Def interacts with Sas10 to form the Def-Sas10-Mpp10 complex to facilitate the Capn3-mediated cleavage of Mpp10. Importantly, we found that Sas10 determines the nucleolar localization of the Mpp10-Imp3-Imp4 complex. In conclusion, Sas10 is essential not only for delivering the Mpp10-Imp3-Imp4 complex to the nucleolus for assembling the SSU processome but also for fine-tuning Mpp10 turnover in the nucleolus during organogenesis.