Structure of stem-loop IV of Tetrahymena telomerase RNA
Structure of stem-loop IV of Tetrahymena telomerase RNA
复制标题
DOI：
10.1038/sj.emboj.7601195
复制
发表时间：
2006-07-12
期刊：
影响因子：
11.4
通讯作者：
Varani, Gabriele
中科院分区：
文献类型：
--
作者：
Chen, Yu;Fender, Jessica;Varani, Gabriele
端粒酶RNA组分中的保守结构域提供了逆转录的模板，将蛋白质组分募集到全酶中，并且是酶活性所需的。在纤毛虫端粒酶RNA中的功能上重要的结构域之一是茎环IV，其强烈刺激端粒酶活性和持续合成能力，即使在反式中提供。四膜虫嗜热茎环IV的NMR结构显示出高度结构化的远端茎环连接到构象灵活的模板近端区域的凸起，严重扭结整个RNA。通过广泛的结构-功能研究，我们确定了有助于这些结构特征和酶活性的残基，对TERT蛋白的结合没有明显的影响。我们建议，由GA凸起和模板近端区域的灵活性引起的弯曲允许在催化循环期间定位预结构化的顶端环。
Conserved domains within the RNA component of telomerase provide the template for reverse transcription, recruit protein components to the holoenzyme and are required for enzymatic activity. Among the functionally essential domains in ciliate telomerase RNA is stem-loop IV, which strongly stimulates telomerase activity and processivity even when provided in trans. The NMR structure of Tetrahymena thermophila stem-loop IV shows a highly structured distal stem-loop linked to a conformationally flexible template-proximal region by a bulge that severely kinks the entire RNA. Through extensive structure-function studies, we identify residues that contribute to both these structural features and to enzymatic activity, with no apparent effect on the binding of TERT protein. We propose that the bending induced by the GA bulge and the flexibility of the template-proximal region allow positioning of the prestructured apical loop during the catalytic cycle.