近日，美国RNA治疗研究所研究团队报道了天然RNA纳米笼的低温电镜结构。该研究于2025年6月16日发表于国际一流学术期刊《自然》杂志上。

在这里，小组报告了在细菌和噬菌体基因组中发现的由lncRNA ROOL（瘤胃起源，华丽，大）形成的两个天然RNA纳米笼的结构。~2.9冷冻电镜（cryo-EM）结构显示，ROOL RNA形成直径为28nm、轴向长度为20nm的八微米纳米笼，其中空内部具有无序区域。该八聚体通过许多三级和四级相互作用来稳定，包括该团队建议命名为“A-minor钉”的三链A-minor钉。分离的ROOL单体在~3.2-分辨率表明纳米笼组装涉及链交换机制，导致四元亲和环。最后，研究人员发现，ROOL RNA与RNA适体、tRNA或microRNA结合，保留了其结构，形成了一个具有径向显示货物的纳米笼。因此，他们的发现可能使新型RNA纳米笼的工程设计成为研究和治疗应用的运载工具。

据介绍，长（200个核苷酸）的非编码RNA （lncRNAs）在生命的各个方面发挥着重要作用。通过比较基因组学分析，已经在细菌和噬菌体中发现了20多种lncRNAs，但它们的生物学功能在很大程度上仍未被探索。由于尺寸较大，大多数lncRNAs的结构决定因素也未被表征。

附：英文原文

Title: Cryo-EM structure of a natural RNA nanocage

Author: Ling, Xiaobin, Golovenko, Dmitrij, Gan, Jianhua, Ma, Jinbiao, Korostelev, Andrei A., Fang, Wenwen

Issue&Volume: 2025-06-16

Abstract: Long (>200 nucleotides) non-coding RNAs (lncRNAs) play important roles in diverse aspects of life. Over 20 classes of lncRNAs have been identified in bacteria and bacteriophages through comparative genomics analyses, but their biological functions remain largely unexplored1-3. Due to the large sizes, the structural determinants of most lncRNAs also remain uncharacterized. Here we report the structures of two natural RNA nanocages formed by the lncRNA ROOL (rumen-originating, ornate, large) found in bacterial and phage genomes. ~2.9 cryo-electron microscopy (cryo-EM) structures reveal that ROOL RNAs form an octameric nanocage with a 28-nm diameter and 20-nm axial length, whose hollow inside features poorly ordered regions. The octamer is stabilized by numerous tertiary and quaternary interactions, including triple-strand A-minors that we propose to name “A-minor staples”. The structure of an isolated ROOL monomer at ~3.2- resolution indicates that nanocage assembly involves a strand-swapping mechanism resulting in quaternary kissing loops. Finally, we show that ROOL RNA fused to an RNA aptamer, tRNA, or microRNA retains its structure forming a nanocage with radially displayed cargos. Our findings therefore may enable the engineering of novel RNA nanocages as delivery vehicles for research and therapeutic applications.

DOI: 10.1038/s41586-025-09262-x

Source: https://www.nature.com/articles/s41586-025-09262-x