The ubiquitin hybrid gene UBA52 regulates ubiquitination of ribosome and sustains embryonic development.
The ubiquitin hybrid gene UBA52 regulates ubiquitination of ribosome and sustains embryonic development.
复制标题
DOI：
10.1038/srep36780
复制
发表时间：
2016-11-10
影响因子：
4.6
通讯作者：
Watanabe M
中科院分区：
文献类型：
--
作者：
Kobayashi M;Oshima S;Maeyashiki C;Nibe Y;Otsubo K;Matsuzawa Y;Nemoto Y;Nagaishi T;Okamoto R;Tsuchiya K;Nakamura T;Watanabe M
泛素化是一种重要的翻译后修饰；然而，泛素编码基因的功能仍不清楚。 UBA52 编码包含 N 末端泛素和 C 末端核糖体蛋白 L40 (RPL40) 的融合蛋白。在这里，我们发现 Uba52 缺陷小鼠在胚胎发生过程中死亡。 UBA52 缺陷细胞表现出正常水平的总泛素。然而，UBA52 缺陷细胞表现出蛋白质合成减少和细胞周期停滞。 UBA52 的过度表达改善了由 UBA52 缺陷引起的细胞周期停滞。令人惊讶的是，RPL40 表达本身不足以调节细胞周期蛋白 D 的表达。 RPL40 从 UBA52 上裂解是维持蛋白质合成所必需的。此外，我们发现RPL40与从UBA52切割下来的泛素形成核糖体复合物。 UBA52 同时向核糖体提供 RPL40 和泛素。我们的研究表明，泛素编码基因 UBA52 不仅是泛素库的泛素供应者，而且还是核糖体蛋白复合物的调节因子。这些发现为泛素依赖性翻译和胚胎发育的调节提供了新的见解。
Ubiquitination is a crucial post-translational modification; however, the functions of ubiquitin-coding genes remain unclear. UBA52 encodes a fusion protein comprising ubiquitin at the N-terminus and ribosomal protein L40 (RPL40) at the C-terminus. Here we showed that Uba52-deficient mice die during embryogenesis. UBA52-deficient cells exhibited normal levels of total ubiquitin. However, UBA52-deficient cells displayed decreased protein synthesis and cell-cycle arrest. The overexpression of UBA52 ameliorated the cell-cycle arrest caused by UBA52 deficiency. Surprisingly, RPL40 expression itself is insufficient to regulate cyclin D expression. The cleavage of RPL40 from UBA52 was required for maintaining protein synthesis. Furthermore, we found that RPL40 formed a ribosomal complex with ubiquitin cleaved from UBA52. UBA52 supplies RPL40 and ubiquitin simultaneously to the ribosome. Our study demonstrated that the ubiquitin-coding gene UBA52 is not just an ubiquitin supplier to the ubiquitin pool but is also a regulator of the ribosomal protein complex. These findings provide novel insights into the regulation of ubiquitin-dependent translation and embryonic development.
登录
查看更多内容
影响因子：
64.8
作者：
Oshima, Shigeru;Turer, Emre E.;Callahan, Joseph A.;Chai, Sophia;Advincula, Rommel;Barrera, Julio;Shifrin, Nataliya;Lee, Bettina;Yen, Benjamin;Woo, Tammy;Malynn, Barbara A.;Ma, Averil
通讯作者：
Ma, Averil
影响因子：
23.9
作者：
Sanchez CG;Teixeira FK;Czech B;Preall JB;Zamparini AL;Seifert JR;Malone CD;Hannon GJ;Lehmann R
通讯作者：
Lehmann R
影响因子：
5.3
作者：
Matsson, H;Davey, EJ;Dahl, N
通讯作者：
Dahl, N
影响因子：
16
作者：
Higgins, Renee;Gendron, Joshua M.;Rising, Lisa;Mak, Raymond;Webb, Kristofor;Kaiser, Stephen E.;Zuzow, Nathan;Riviere, Paul;Yang, Bing;Fenech, Emma;Tang, Xin;Lindsay, Scott A.;Christianson, John C.;Hampton, Randolph Y.;Wasserman, Steven A.;Bennett, Eric J.
通讯作者：
Bennett, Eric J.
影响因子：
5.3
作者：
Panic, Linda;Tamarut, Sanda;Volarevic, Sinisa
通讯作者：
Volarevic, Sinisa