Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.
PLoS Genet. 2013;9(8):e1003708. doi: 10.1371/journal.pgen.1003708. Epub 2013 Aug 22.
Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22(-/-) mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22(-/-) mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.
大多数酵母核糖体蛋白基因都被复制，对其特征的研究提出了关于存在具有不同亚基组成或特定功能的特殊核糖体的假说。在酵母中，核糖体蛋白基因通常被复制，有证据表明旁系同源物可能具有特定的功能。与酵母不同，大多数哺乳动物核糖体蛋白被认为是由单个基因拷贝编码的，这增加了核糖体异质群体是酵母特有的可能性。在这里，我们研究了哺乳动物 Rpl22 的作用，发现 Rpl22(-/-) 小鼠只有细微的表型，没有明显的翻译缺陷。我们发现，在 Rpl22(-/-) 小鼠中，Rpl22 样 1 (Rpl22l1) 的表达和掺入核糖体的代偿性增加。与核糖体蛋白都可以支持翻译的假说一致，Rpl22l1 的敲低会损害缺乏 Rpl22 的细胞的生长。从机制上讲，Rpl22 通过结合内部发夹结构并抑制其表达来直接调节 Rpl22l1。我们提出，哺乳动物中可能存在核糖体特异性，这为一个核糖体蛋白可以通过调节其自身的旁系同源物来影响核糖体的组成提供了证据。
