Couté Yohann, Kindbeiter Karine, Belin Stéphane, Dieckmann Régis, Duret Laurent, Bezin Laurent, Sanchez Jean-Charles, Diaz Jean-Jacques
Biomedical Proteomics Research Group, Département de Biologie Structurale et Bioinformatique, Centre Médical Universitaire, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland.
Mol Cell Proteomics. 2008 Mar;7(3):546-59. doi: 10.1074/mcp.M700510-MCP200. Epub 2007 Dec 6.
Proteomics analyses of human nucleoli provided molecular bases for an understanding of the multiple functions fulfilled by these nuclear domains. However, the biological roles of about 100 of the identified proteins are unpredictable. The present study describes the functional characterization of one of these proteins, ISG20L2. We demonstrate that ISG20L2 is a 3' to 5' exoribonuclease involved in ribosome biogenesis at the level of 5.8 S rRNA maturation, more specifically in the processing of the 12 S precursor rRNA. The use of truncated forms of ISG20L2 demonstrated that its N-terminal half promotes the nucleolar localization and suggested that its C-terminal half bears the exoribonuclease activity. Identification of the binding partners of ISG20L2 confirmed its involvement in the biogenesis of the large ribosomal subunit. These results strongly support the notion that, in human, as it was demonstrated in yeast, 5.8 S rRNA maturation requires several proteins in addition to the exosome complex. Furthermore this observation greatly sustains the idea that the extremely conserved need for correctly processed rRNAs in vertebrates and yeast is achieved by close but different mechanisms.
对人类核仁的蛋白质组学分析为理解这些核结构域所履行的多种功能提供了分子基础。然而，所鉴定出的约100种蛋白质的生物学作用是不可预测的。本研究描述了其中一种蛋白质ISG20L2的功能特性。我们证明，ISG20L2是一种3'至5'外切核糖核酸酶，在5.8 S rRNA成熟水平上参与核糖体生物合成，更具体地说是在12 S前体rRNA的加工过程中。使用ISG20L2的截短形式表明其N端促进核仁定位，并表明其C端具有外切核糖核酸酶活性。对ISG20L2结合伙伴的鉴定证实了其参与大核糖体亚基的生物合成。这些结果有力地支持了这样一种观点，即在人类中，正如在酵母中所证明的那样，5.8 S rRNA成熟除了需要外泌体复合物外，还需要几种蛋白质。此外，这一观察结果极大地支持了这样一种观点，即脊椎动物和酵母中对正确加工的rRNA的极度保守需求是通过密切但不同的机制实现的。
