摘要
During ribosome biogenesis,the small subunit(SSU)processome is responsible for 40S assembly.The BMS1/RCL1 complex is a core component of the SSU processome that plays an important role in 18S rRNA processing and maturation.Genetic studies using zebrafish mutants indicate that both Bms1-like(Bms1l)and Rcl1 are essential for digestive organ development.In spite of vital functions of this complex,the mutual dependence of these two nucleolar proteins for the stability and function remains elusive.In this study,we identified an RCL1-interacting domain in BMS1,which is conserved in zebrafish and humans.Moreover,both the protein stability and nucleolar entry of RCL1 depend on its interaction with BMS1,otherwise RCL1 degraded through the ubiquitination-proteasome pathway.Functional studies revealed that overexpression of RCL1 in BMS1-knockdown cells can partially rescue the defects in 18S rRNA processing and cell proliferation,and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1l^(sq163/sq163)but not in the knockout mutant bms1l^(zju1/zju1),which is attributed to the nucleolar entry of Rcl1 in the former mutant.Our data demonstrate that BMS1 and RCL1 interaction is essential for not only pre-rRNA processing but also the communication between ribosome biogenesis and cell cycle regulation.
基金
This work was supported by grants fromthe National Natural Science Foundation of China(31771596 and 32000565)。