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

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.
(© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)