H/ACA RNA蛋白质复合物是普遍存在于真核生物和古细菌的一类保守的分子，它们主要介导RNA的假尿嘧啶修饰，同时参与真核生物核糖体的装配和脊椎动物端粒的合成。目前对古细菌H/ACA 复合物的结构己有详细的了解，但对真核生物复合物的结构还了解很少。
2011年11月15日，北京生命科学研究所的叶克穷实验室在《Genes & Development》杂志发表了题为“Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase”的论文。
该论文首次利用重组表达的蛋白质和RNA在体外组装了有催化活性的酵母H/ACA复合物。利用这个重组系统，作者对H/ACA复合物的组装方式、催化活性和三维结构进行了深入的分析。他们解析了包含其中三个蛋白质组分的亚复合物的晶体结构，并分析了复合物结构和功能的关系，发现了许多真核生物H/ACA复合物特有的结构特征。
该研究所博士研究生李爽是该论文的第一作者，段景琦博士、李丹丹、杨兵、董梦秋博士等人也参与了此研究工作。叶克穷博士是本文通讯作者。此项研究受中国科技部和北京市科委资助，在北京生命科学研究所完成。(生物谷 Bioon.com)
doi:10.1101/gad.175299.111
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Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase
Shuang Li, Jingqi Duan, Dandan Li, Bing Yang, Mengqiu Dong and Keqiong Ye,
Box H/ACA ribonucleoprotein particles (RNPs) mediate pseudouridine synthesis, ribosome formation, and telomere maintenance. The structure of eukaryotic H/ACA RNPs remains poorly understood. We reconstituted functional Saccharomyces cerevisiae H/ACA RNPs with recombinant proteins Cbf5, Nop10, Gar1, and Nhp2 and a two-hairpin H/ACA RNA; determined the crystal structure of a Cbf5, Nop10, and Gar1 ternary complex at 1.9 Å resolution; and analyzed the structure–function relationship of the yeast complex. Although eukaryotic H/ACA RNAs have a conserved two-hairpin structure, isolated single-hairpin RNAs are also active in guiding pseudouridylation. Nhp2, unlike its archaeal counterpart, is largely dispensable for the activity, reflecting a functional adaptation of eukaryotic H/ACA RNPs to the variable RNA structure that Nhp2 binds. The N-terminal extension of Cbf5, a hot spot for dyskeratosis congenita mutation, forms an extra structural layer on the PUA domain. Gar1 is distinguished from the assembly factor Naf1 by containing a C-terminal extension that controls substrate turnover and the Gar1–Naf1 exchange during H/ACA RNP maturation. Our results reveal significant novel features of eukaryotic H/ACA RNPs.
