Stability and function of RCL1 are dependent on interaction with BMS1.

During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1l (Bms1-like) and Rcl1 are essential for digestive organs development. In spite of the vital functions of this complex, the mutual dependence for the stability and function of these two nucleolar proteins remains elusive. In this study, we identified an RCL1-interacting domain in BMS1 conserved in zebrafish and human. Moreover, both protein stability and nucleolar entry of RCL1 depend on BMS1, otherwise leading to RCL1 degradation through the ubiquitination-proteasome pathway. Functional studies reveal that overexpression of RCL1 in BMS1 knockdown cells can partially rescue the defects of 18S rRNA processing and cell proliferation, and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1lsq163/sq163but not the knockout mutant bms1lzju1/zju1, attributed to the nucleolar entry of Rcl1 in the former. Our data demonstrate that BMS1 and RCL1 interaction is essential not only for pre-rRNA processing but also for the communication between ribosome biogenesis and cell cycle regulation.