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内含子活性位点的结构分析及对剪接体的影响。

A structural analysis of the group II intron active site and implications for the spliceosome.

机构信息

Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.

出版信息

RNA. 2010 Jan;16(1):1-9. doi: 10.1261/rna.1791310. Epub 2009 Nov 30.

DOI:10.1261/rna.1791310
PMID:19948765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2802019/
Abstract

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.

摘要

内含子 II 是自我剪接的可移动遗传元件,它们从根本上影响了陆地基因组的结构。这些大型核酶在几乎所有形式的细菌和真核生物中对于基因表达仍然很重要,并且它们被认为与真核剪接体具有共同的祖先,后者是加工所有核前体 mRNA 所必需的。通过 X 射线晶体学最近确定了一个内含子 IIIC 的三维结构,使得能够可视化活性位点和稳定分子的精细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,并评估了它们与内含子 II 先前的生化、遗传和系统发育分析的对应关系。此外,我们评估了内含子核心内 RNA 模体的结构意义,例如主沟三螺旋和域 5 凸起。在结合了已知的内含子 II 核心信息后,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。这种分析导致了一组关于剪接体活性位点的分子结构的预测。

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本文引用的文献

1
Tertiary architecture of the Oceanobacillus iheyensis group II intron.海洋芽孢杆菌Ⅱ类内含子的三级结构。
RNA. 2010 Jan;16(1):57-69. doi: 10.1261/rna.1844010. Epub 2009 Dec 1.
2
Structural insights into RNA splicing.RNA剪接的结构见解。
Curr Opin Struct Biol. 2009 Jun;19(3):260-6. doi: 10.1016/j.sbi.2009.04.002. Epub 2009 May 13.
3
Structural basis for exon recognition by a group II intron.II 型内含子识别外显子的结构基础。
Nat Struct Mol Biol. 2008 Nov;15(11):1221-2. doi: 10.1038/nsmb.1509. Epub 2008 Oct 26.
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Solution structure and dynamics of the wild-type pseudoknot of human telomerase RNA.人端粒酶RNA野生型假结的溶液结构与动力学
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5
The GANC tetraloop: a novel motif in the group IIC intron structure.甘氨酰胺核苷酸(GAN)四环:IIC类内含子结构中的一种新基序。
J Mol Biol. 2008 Nov 14;383(3):475-81. doi: 10.1016/j.jmb.2008.08.043. Epub 2008 Aug 26.
6
Computational screen for spliceosomal RNA genes aids in defining the phylogenetic distribution of major and minor spliceosomal components.剪接体RNA基因的计算筛选有助于确定主要和次要剪接体成分的系统发育分布。
Nucleic Acids Res. 2008 May;36(9):3001-10. doi: 10.1093/nar/gkn142. Epub 2008 Apr 4.
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Crystal structure of a self-spliced group II intron.一种自我剪接的II类内含子的晶体结构。
Science. 2008 Apr 4;320(5872):77-82. doi: 10.1126/science.1153803.
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Structure of the SAM-II riboswitch bound to S-adenosylmethionine.与S-腺苷甲硫氨酸结合的SAM-II核糖开关的结构。
Nat Struct Mol Biol. 2008 Feb;15(2):177-82. doi: 10.1038/nsmb.1371. Epub 2008 Jan 20.
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