Self-Assembly of Intracellular Multivalent RNA Complexes Using Dimeric Corn and Beetroot Aptamers.

Self-Assembly of Intracellular Multivalent RNA Complexes Using Dimeric Corn and Beetroot Aptamers.
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使用二聚玉米和甜菜根适体的细胞内多价RNA复合物的自组装。

DOI:
10.1021/jacs.1c13583
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发表时间:
2022-03-30
影响因子:
15
通讯作者:
Jaffrey, Samie R.
Jaffrey, Samie R.
中科院分区:
化学1区
文献类型:
--
作者:
Wu, Jiahui;Svensen, Nina;Song, Wenjiao;Kim, Hyaeyeong;Zhang, Sulei;Li, Xing;Jaffrey, Samie R.

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DNA和RNA可以自发地自组装成各种结构,包括聚集体、复合体和有序结构。由于目前的自组装方法产生的双链核酸是不稳定的,并激活了天然的RNA免疫途径,因此自组装反应不能在遗传编码中发生在活的哺乳动物细胞中。在这里,我们展示了最近描述的二聚体适配子可以用来创建自组装的RNA,并在细胞中创建RNA组装件和RNA-蛋白质组装件。我们发现,将五个副本的玉米(一种二聚体荧光RNA适配子)掺入一个RNA中,会导致RNA在细胞中形成大的簇,反映由这些RNA实现的多价RNA-RNA相互作用。在这里,我们还描述了第二个二聚体荧光适配子,甜菜根,它显示了与玉米的部分序列相似性。玉米和甜菜根自身形成同源二聚体,但不形成玉米-甜菜根异二聚体。因此,我们使用玉米和甜菜根在同一细胞中编码不同的RNA-蛋白质组合。总体而言,这些研究提供了一种诱导RNA自组装的方法,使细胞中不同的RNA组装成为可能,并证明蛋白质可以被招募到RNA组装中,以遗传编码细胞内的RNA-蛋白质组装。作者被要求提交目录(TOC)的图形条目,与手稿标题结合在一起,应该给读者以下其中一个具有代表性的想法:手稿中讨论的关键结构、反应、方程、概念或定理等。有关TOC图形规范,请参阅该杂志的作者说明。
DNA and RNA can spontaneously self-assemble into various structures, including aggregates, complexes, and ordered structures. The self-assembly reactions cannot be genetically encoded to occur in living mammalian cells since the double-stranded nucleic acids generated by current self-assembly approaches are unstable and activate innate RNA immunity pathways. Here, we show that recently described dimeric aptamers can be used to create RNAs that self-assemble and create RNA assemblies and RNA-protein assemblies in cells. We find that incorporation of five copies of Corn, a dimeric fluorogenic RNA aptamer, into an RNA causes the RNA to form large clusters in cells, reflecting multivalent RNA-RNA interactions enabled by these RNAs. Here, we also describe a second dimeric fluorogenic aptamer, Beetroot, which shows partial sequence similarity to Corn. Both Corn and Beetroot form homodimers with themselves, but do not form Corn-Beetroot heterodimers. We thus use Corn and Beetroot to encode distinct RNA-protein assemblies in the same cells. Overall, these studies provide an approach for inducing RNA self-assembly, enable multiplexing of distinct RNA assemblies in cells, and demonstrate that proteins can be recruited to RNA assemblies to genetically encode intracellular RNA-protein assemblies. Authors are required to submit a graphic entry for the Table of Contents (TOC) that, in conjunction with the manuscript title, should give the reader a representative idea of one of the following: A key structure, reaction, equation, concept, or theorem, etc., that is discussed in the manuscript. Consult the journal’s Instructions for Authors for TOC graphic specifications.
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发表时间: 2011-07-29
期刊: Science (New York, N.Y.)
影响因子: --
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