Stability and function of RCL1 are dependent on the interaction with BMS1
Stability and function of RCL1 are dependent on the interaction with BMS1
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DOI：
10.1093/jmcb/mjad046
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发表时间：
2024-04-17
影响因子：
5.5
通讯作者：
Lo，Li Jan
中科院分区：
文献类型：
--
作者：
Wang，Yong;Zhao，Zhenyu;Lo，Li Jan
在核糖体生物发生过程中，小亚基 (SSU) 加工组负责 40S 组装。 BMS1/RCL1 复合物是 SSU 加工组的核心组成部分，在 18S rRNA 加工和成熟中发挥着重要作用。使用斑马鱼突变体的遗传学研究表明，Bms1 样 (Bms1l) 和 Rcl1 对于消化器官发育至关重要。尽管该复合物具有重要的功能，但这两种核仁蛋白的稳定性和功能的相互依赖性仍然难以捉摸。在这项研究中，我们在 BMS1 中发现了一个 RCL1 相互作用域，该域在斑马鱼和人类中是保守的。此外，RCL1的蛋白质稳定性和核仁进入都取决于其与BMS1的相互作用，否则RCL1会通过泛素化-蛋白酶体途径降解。功能研究表明，在BMS1敲除细胞中过表达RCL1可以部分挽救18S rRNA加工和细胞增殖的缺陷，并且肝细胞特异性过表达Rcl1可以在bms1l替代突变体bms1lsq163/sq163中恢复斑马鱼肝脏发育，但在敲除突变体bms1lzju1/zju1中则不能，这归因于Rcl1在前者中进入核仁突变体。我们的数据表明，BMS1 和 RCL1 相互作用不仅对于前 rRNA 加工至关重要，而且对于核糖体生物发生和细胞周期调控之间的通讯也至关重要。
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 thebms1lsubstitution mutantbms1lsq163/sq163but not in the knockout mutantbms1lzju1/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.