H/ACA small nucleolar RNA pseudouridylation pockets bind substrate RNA to form three-way junctions that position the target U for modification
H/ACA small nucleolar RNA pseudouridylation pockets bind substrate RNA to form three-way junctions that position the target U for modification
复制标题
DOI：
10.1073/pnas.0701534104
复制
发表时间：
2007-04-17
影响因子：
11.1
通讯作者：
Feigon, Juli
中科院分区：
文献类型：
--
作者：
Wu, Haihong;Feigon, Juli
在真核生物核糖体RNA（rRNA）和剪接体小核RNA（snRNA）的生物合成过程中，特定位点的尿苷被H/ACA核糖核蛋白颗粒（RNP）转化为假尿苷。每个H/ACA RNP含有底物特异性H/ACA RNA和四种常见蛋白质，假尿苷合酶Cbf5，Nop10，Gar1和Nhp2。H/ACA RNA含有至少一个假尿苷化（psi）口袋，其与靶尿苷侧翼的序列互补。在这篇文章中，我们展示了结构证据，psi口袋可以在没有蛋白质成分的情况下与底物RNA形成预测的碱基对。本文报道了人U65 H/ACA小核仁RNA（snoRNA）3 ′ psi口袋中的RNA发夹与底物rRNA形成的复合物的溶液结构。snoRNA-rRNA底物复合物具有独特的结构，具有两个偏移的平行堆叠螺旋对和两个不寻常的分子间三通接头，它们一起组织底物以对接到Cbf5的活性位点。底物RNA在复合物中snoRNA的一面上相互作用，形成一个可以容易地容纳在H/ACA RNP中的结构，并解释了连续的底物RNA如何加载到RNP中的H/ACA RNA上和从RNP中卸载。
During the biogenesis of eukaryotic ribosomal RNA (rRNA) and spliceosomal small nuclear RNA (snRNA), uridines at specific sites are converted to pseudouridines by H/ACA ribonucleoprotein particles (RNPs). Each H/ACA RNP contains a substrate-specific H/ACA RNA and four common proteins, the pseudouridine synthase Cbf5, Nop10, Gar1, and Nhp2. The H/ACA RNA contains at least one pseudouridylation (psi) pocket, which is complementary to the sequences flanking the target uridine. in this article, we show structural evidence that the psi pocket can form the predicted base pairs with substrate RNA in the absence of protein components. We report the solution structure of the complex between an RNA hairpin derived from the 3 ' psi pocket of human U65 H/ACA small nucleolar RNA (snoRNA) and the substrate rRNA. The snoRNA-rRNA substrate complex has a unique structure with two offset parallel pairs of stacked helices and two unusual intermolecular three-way junctions, which together organize the substrate for docking into the active site of Cbf5. The substrate RNA interacts on one face of the snoRNA in the complex, forming a structure that easily could be accommodated in the H/ACA RNP, and explains how successive substrate RNAs could be loaded onto and unloaded from the H/ACA RNA in the RNP.