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异三聚体前体 mRNA 滞留和剪接复合物的协同结构。

Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex.

机构信息

Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

出版信息

Nat Struct Mol Biol. 2014 Oct;21(10):911-8. doi: 10.1038/nsmb.2889. Epub 2014 Sep 14.

DOI:10.1038/nsmb.2889
PMID:25218446
Abstract

The precursor mRNA (pre-mRNA) retention and splicing (RES) complex is a spliceosomal complex that is present in yeast and humans and is important for RNA splicing and retention of unspliced pre-mRNA. Here, we present the solution NMR structure of the RES core complex from Saccharomyces cerevisiae. Complex formation leads to an intricate folding of three components-Snu17p, Bud13p and Pml1p-that stabilizes the RNA-recognition motif (RRM) fold of Snu17p and increases binding affinity in tertiary interactions between the components by more than 100-fold compared to that in binary interactions. RES interacts with pre-mRNA within the spliceosome, and through the assembly of the RES core complex RNA binding efficiency is increased. The three-dimensional structure of the RES core complex highlights the importance of cooperative folding and binding in the functional organization of the spliceosome.

摘要

前体 mRNA(pre-mRNA)保留和剪接(RES)复合物是一种剪接体复合物,存在于酵母和人类中,对 RNA 剪接和未剪接的 pre-mRNA 的保留很重要。在这里,我们展示了来自酿酒酵母的 RES 核心复合物的溶液 NMR 结构。复合物的形成导致三个成分-Snu17p、Bud13p 和 Pml1p-的复杂折叠,稳定了 Snu17p 的 RNA 识别基序(RRM)折叠,并通过超过 100 倍的增加了组件之间的三级相互作用的结合亲和力与二元相互作用相比。RES 与剪接体中的 pre-mRNA 相互作用,并且通过组装 RES 核心复合物,RNA 结合效率增加。RES 核心复合物的三维结构突出了协同折叠和结合在剪接体功能组织中的重要性。

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