A structural analysis of the group II intron active site and implications for the spliceosome
A structural analysis of the group II intron active site and implications for the spliceosome
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DOI：
10.1261/rna.1791310
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发表时间：
2010-01-01
期刊：
影响因子：
4.5
通讯作者：
Pyle, Anna Marie
中科院分区：
文献类型：
--
作者：
Keating, Kevin S.;Toor, Navtej;Pyle, Anna Marie
第二组内含子是自剪接的、可移动的遗传元件，从根本上影响了陆地基因组的组织。这些大的核酶对几乎所有形式的细菌和真核生物的基因表达仍然是重要的，它们被认为与处理所有核前mRNAs所需的真核剪接体有共同的祖先。最近，X射线结晶学确定了一组IIC内含子的三维结构，这使得人们有可能看到稳定分子的活性部位和复杂的三级相互作用网络。在这里，我们详细描述了活性位点的分子特征，并评估了它们与先前关于第二组内含子的生化、遗传和系统发育分析的一致性。此外，我们还评估了内含子核心中的RNA基序的结构意义，如主槽三螺旋和结构域5凸起。在结合了关于第二组内含子核心的已知内容后，我们将其与真核剪接体中U6 SnRNA的已知结构特征进行了比较。这一分析导致了对剪接体活性部位分子结构的一系列预测。
Group II introns are self-splicing, mobile genetic elements that have fundamentally influenced the organization of terrestrial genomes. These large ribozymes remain important for gene expression in almost all forms of bacteria and eukaryotes and they are believed to share a common ancestry with the eukaryotic spliceosome that is required for processing all nuclear pre-mRNAs. The three-dimensional structure of a group IIC intron was recently determined by X-ray crystallography, making it possible to visualize the active site and the elaborate network of tertiary interactions that stabilize the molecule. Here we describe the molecular features of the active site in detail and evaluate their correspondence with prior biochemical, genetic, and phylogenetic analyses on group II introns. In addition, we evaluate the structural significance of RNA motifs within the intron core, such as the major-groove triple helix and the domain 5 bulge. Having combined what is known about the group II intron core, we then compare it with known structural features of U6 snRNA in the eukaryotic spliceosome. This analysis leads to a set of predictions for the molecular structure of the spliceosomal active site.