波士顿大学医学院Ruslan Aphasizhev团队的一项最新研究提出了锥虫线粒体RNA编辑级联的结构基础。2026年7月22日出版的《自然》发表了这项成果。

该研究组将编辑体定义为由RNA编辑底物结合复合体（RESC）和RNA编辑催化复合体1或2 (RECC1或RECC2)6组成的超分子组装体，并给出了大约1-MDa的RECC1和RECC2的低温电镜结构。这些核糖核蛋白与蜻蜓相似，具有头部、胸状核、尾巴和翅膀，分别介导尿苷缺失和尿苷插入级联反应。在每个RECC中，包含一个活性和三个非活性RNase III结构域的四聚体核心捕获引导RNA (gRNA) -mRNA双链，而辅助锌指区分缺失位点和插入位点并定位mRNA切割的底物（步骤1）。三个外周寡核苷酸结合折叠异四聚体灵活地附着在核心上，形成一个空间适应性强的反应室。尾巴招募核酸外切酶和尿苷基转移酶来去除或添加尿苷（步骤II），而翅膀由一个结构tRNA协调，定位RNA连接酶来密封编辑的mRNA（步骤III）。总之，这些结构揭示了gRNA导向的底物识别、mRNA切割、尿苷缺失、插入和连接如何集成在一个大分子机器中。这种结构定义了RNA编辑中信息传递的机制。

据介绍，由于潜在的多酶机制具有高度动态性，所以在锥虫线粒体中尿苷插入和删除mRNA编辑的分子机制仍不清楚。

附：英文原文

Title: Structural basis of the RNA-editing cascade in trypanosome mitochondria

Author: Liu, Yun-Tao, Vacas, Andres F., Jih, Jonathan, Zhao, Xiaojing, Yu, Clinton, Lee, Jane K. J., Suematsu, Takuma, Solayman, Md, Wang, Hong, Wang, Xiaorong, Huang, Lan, Zhang, Liye, Aphasizheva, Inna, Zhou, Z. Hong, Aphasizhev, Ruslan

Issue&Volume: 2026-07-22

Abstract: The molecular mechanism of uridine insertion-and-deletion mRNA editing in trypanosome mitochondria1,2,3,4 has remained unclear because of the highly dynamic nature of the underlying multi-enzyme machinery5. Here, we define editosomes as supramolecular assemblies formed by the RNA-editing substrate-binding complex (RESC) and either RNA-editing catalytic complex 1 or 2 (RECC1 or RECC2)6, and present cryo-electron microscopy structures of the approximately 1-MDa RECC1 and RECC2. Resembling dragonflies, with a head, thorax-like core, tail and wings, these ribonucleoproteins mediate the uridine deletion and uridine insertion cascades, respectively. In each RECC, a tetrameric core containing one active and three inactive RNase III domains captures the guide RNA (gRNA)–mRNA duplex, while auxiliary zinc fingers distinguish deletion sites from insertion sites and position the substrate for mRNA cleavage (step I). Three peripheral oligonucleotide-binding-fold heterotetramers are flexibly attached to the core, forming a spatially adaptable reaction chamber. The tail recruits the exonuclease and uridylyltransferase that remove or add uridines (step II), whereas the wings, coordinated by an architectural tRNA, position RNA ligases to seal the edited mRNA (step III). Together, these structures reveal how gRNA-directed substrate recognition, mRNA cleavage, uridine deletion and insertion and ligation are integrated in a single macromolecular machine. This architecture defines the mechanism of information transfer in RNA editing.

DOI: 10.1038/s41586-026-10831-x

Source: https://www.nature.com/articles/s41586-026-10831-x