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.