Downing Maureen E, Brady Kristina L, Caprara Mark G
Center for RNA Molecular Biology, Case Western Reserve University, School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4960, USA.
RNA. 2005 Apr;11(4):437-46. doi: 10.1261/rna.7225205.
Group I introns often encode proteins that catalyze site-specific DNA hydrolysis. Some of these proteins have acquired the ability to promote splicing of their cognate intron, but whether these two activities reside in different regions of the protein remains obscure. A crystal structure of I-AniI, a dual function intron-encoded protein, has shown that the protein has two pseudo-symmetric domains of equal size. Each domain contacts its DNA substrate on either side of two cleavage sites. As a first step to identify the RNA binding surface, the N- and C-terminal domains of I-AniI were separately expressed and tested for promoting the splicing of the mitochondrial (mt) COB pre-RNA. The N-terminal protein showed no splicing activation or RNA binding, suggesting that this domain plays a minimal role in activity or is improperly folded. Remarkably, the 16-kDa C-terminal half facilitates intron splicing with a rate similar to that of the full-length protein. Both the C-terminal fragment and full-length proteins bind tightly to the COB intron. RNase footprinting shows that the C-terminal and full-length proteins bind to the same regions and induce the same conformational changes in the COB intron. Together, these results show that the C-terminal fragment of I-AniI is necessary and sufficient for maturase activity and suggests that I-AniI acquired splicing function by utilizing a relatively small protein surface that likely represents a novel RNA binding motif. This fragment of I-AniI represents the smallest group I intron splicing cofactor described to date.
I 组内含子通常编码催化位点特异性 DNA 水解的蛋白质。其中一些蛋白质已获得促进其同源内含子剪接的能力,但这两种活性是否存在于蛋白质的不同区域仍不清楚。I-AniI 是一种具有双重功能的内含子编码蛋白,其晶体结构表明该蛋白有两个大小相等的假对称结构域。每个结构域在两个切割位点的两侧与 DNA 底物接触。作为确定 RNA 结合表面的第一步,I-AniI 的 N 端和 C 端结构域被分别表达,并测试其促进线粒体(mt)COB 前体 RNA 剪接的能力。N 端蛋白未显示出剪接激活或 RNA 结合能力,这表明该结构域在活性方面作用极小或折叠不当。值得注意的是,16 kDa 的 C 端半段促进内含子剪接的速率与全长蛋白相似。C 端片段和全长蛋白都能紧密结合 COB 内含子。核糖核酸酶足迹分析表明,C 端和全长蛋白结合到相同区域,并在 COB 内含子中诱导相同的构象变化。这些结果共同表明,I-AniI 的 C 端片段对于成熟酶活性是必要且充分的,这表明 I-AniI 通过利用一个可能代表新型 RNA 结合基序的相对较小的蛋白质表面获得了剪接功能。I-AniI 的这个片段代表了迄今为止描述的最小的 I 组内含子剪接辅因子。