Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2012;7(9):e43786. doi: 10.1371/journal.pone.0043786. Epub 2012 Sep 12.
Ribosome biogenesis in eukaryotes requires coordinated folding and assembly of a pre-rRNA into sequential pre-rRNA-protein complexes in which chemical modifications and RNA cleavages occur. These processes require many small nucleolar RNAs (snoRNAs) and proteins. Rbm19/Mrd1 is one such protein that is built from multiple RNA-binding domains (RBDs). We find that Rbm19/Mrd1 with five RBDs is present in all branches of the eukaryotic phylogenetic tree, except in animals and Choanoflagellates, that instead have a version with six RBDs and Microsporidia which have a minimal Rbm19/Mrd1 protein with four RBDs. Rbm19/Mrd1 therefore evolved as a multi-RBD protein very early in eukaryotes. The linkers between the RBDs have conserved properties; they are disordered, except for linker 3, and position the RBDs at conserved relative distances from each other. All but one of the RBDs have conserved properties for RNA-binding and each RBD has a specific consensus sequence and a conserved position in the protein, suggesting a functionally important modular design. The patterns of evolutionary conservation provide information for experimental analyses of the function of Rbm19/Mrd1. In vivo mutational analysis confirmed that a highly conserved loop 5-β4-strand in RBD6 is essential for function.
真核生物的核糖体生物发生需要协调折叠和组装前 rRNA 成顺序前 rRNA-蛋白复合物，其中发生化学修饰和 RNA 切割。这些过程需要许多小核仁 RNA（snoRNA）和蛋白质。Rbm19/Mrd1 就是这样一种由多个 RNA 结合结构域（RBD）组成的蛋白质。我们发现，具有五个 RBD 的 Rbm19/Mrd1 存在于真核生物系统发育树的所有分支中，除了动物和领鞭毛虫外，它们具有六个 RBD 的版本，而微孢子虫则具有最小的 Rbm19/Mrd1 蛋白，具有四个 RBD。因此，Rbm19/Mrd1 作为一种多 RBD 蛋白在真核生物中很早就进化了。RBD 之间的接头具有保守特性；它们是无规卷曲的，除了接头 3 外，并且将 RBD 定位在彼此之间的保守相对距离处。除了一个 RBD 外，所有 RBD 都具有 RNA 结合的保守特性，每个 RBD 在蛋白质中都具有特定的共识序列和保守位置，这表明其具有功能上重要的模块化设计。进化保守性的模式为 Rbm19/Mrd1 功能的实验分析提供了信息。体内突变分析证实，RBD6 中高度保守的环 5-β4-链对于功能至关重要。
