Mitrovich Quinn M, Guthrie Christine
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143-2200, USA.
RNA. 2007 Dec;13(12):2066-80. doi: 10.1261/rna.766607. Epub 2007 Oct 23.
The spliceosome is a large, dynamic ribonuclear protein complex, required for the removal of intron sequences from newly synthesized eukaryotic RNAs. The spliceosome contains five essential small nuclear RNAs (snRNAs): U1, U2, U4, U5, and U6. Phylogenetic comparisons of snRNAs from protists to mammals have long demonstrated remarkable conservation in both primary sequence and secondary structure. In contrast, the snRNAs of the hemiascomycetous yeast Saccharomyces cerevisiae have highly unusual features that set them apart from the snRNAs of other eukaryotes. With an emphasis on the pathogenic yeast Candida albicans, we have now identified and compared snRNAs from newly sequenced yeast genomes, providing a perspective on spliceosome evolution within the hemiascomycetes. In addition to tracing the origins of previously identified snRNA variations present in Saccharomyces cerevisiae, we have found numerous unexpected changes occurring throughout the hemiascomycetous lineages. Our observations reveal interesting examples of RNA and protein coevolution, giving rise to altered interaction domains, losses of deeply conserved snRNA-binding proteins, and unique snRNA sequence changes within the catalytic center of the spliceosome. These same yeast lineages have experienced exceptionally high rates of intron loss, such that modern hemiascomycetous genomes contain introns in only approximately 5% of their genes. Also, the splice site sequences of those introns that remain adhere to an unusually strict consensus. Some of the snRNA variations we observe may thus reflect the altered intron landscape with which the hemiascomycetous spliceosome must contend.
剪接体是一种大型的动态核糖核蛋白复合体，负责从新合成的真核RNA中去除内含子序列。剪接体包含五种必需的小核RNA（snRNA）：U1、U2、U4、U5和U6。长期以来，对原生生物到哺乳动物的snRNA进行系统发育比较表明，其一级序列和二级结构都具有显著的保守性。相比之下，半子囊菌酵母酿酒酵母的snRNA具有高度不寻常的特征，使其与其他真核生物的snRNA区分开来。我们现在重点关注致病性酵母白色念珠菌，鉴定并比较了新测序酵母基因组中的snRNA，从而对半子囊菌中的剪接体进化有了一定的认识。除了追溯酿酒酵母中先前鉴定的snRNA变异的起源，我们还发现整个半子囊菌谱系中发生了许多意想不到的变化。我们的观察揭示了RNA和蛋白质共同进化的有趣例子，导致相互作用结构域发生改变、深度保守的snRNA结合蛋白丢失，以及剪接体催化中心内独特的snRNA序列变化。这些相同的酵母谱系经历了异常高的内含子丢失率，以至于现代半子囊菌基因组中只有约5%的基因含有内含子。此外，那些保留下来的内含子的剪接位点序列遵循异常严格的共有序列。因此，我们观察到的一些snRNA变异可能反映了半子囊菌剪接体必须应对的内含子格局的改变。
