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杂交RNA/DNA串联体与自限性复合物:结构及治疗应用前景

Hybrid RNA/DNA Concatemers and Self-Limited Complexes: Structure and Prospects for Therapeutic Applications.

作者信息

Kanarskaya Maria A, Novikova Sofia V, Lomzov Alexander A

机构信息

Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia.

Department of Physics, Novosibirsk State University, Novosibirsk 630090, Russia.

出版信息

Molecules. 2024 Dec 13;29(24):5896. doi: 10.3390/molecules29245896.

DOI:10.3390/molecules29245896
PMID:39769985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11677838/
Abstract

The development of new convenient tools for the design of multicomponent nucleic acid (NA) complexes is one of the challenges in biomedicine and NA nanotechnology. In this paper, we analyzed the formation of hybrid RNA/DNA concatemers and self-limited complexes by a pair of oligonucleotides using UV melting, circular dichroism spectroscopy, and a gel shift assay. Effects of the size of the linker between duplex-forming segments of the oligonucleotides on complexes' shape and number of subunits were compared and systematized for RNA/DNA, DNA/DNA, and RNA/RNA assemblies. The data on complex types summarized here as heat maps offer a convenient tool for the design of NA constructs. General rules found for RNA/DNA, DNA/DNA, and RNA/RNA complexes allow not only designing complexes with desired structures but also purposefully transforming their geometry. The A-form of the double helix of the studied RNA/DNA complexes was confirmed by circular dichroism analysis. Moreover, we show for the first time efficient degradation of RNA in hybrid self-limited complexes by RNase H and imidazole. The results open up new prospects for the design of supramolecular complexes as tools for nanotechnology, nanomachinery, and biomedical applications.

摘要

开发用于设计多组分核酸(NA)复合物的新型便捷工具是生物医学和NA纳米技术面临的挑战之一。在本文中,我们使用紫外熔解、圆二色光谱和凝胶迁移分析,分析了一对寡核苷酸形成杂交RNA/DNA串联体和自限性复合物的情况。比较并系统研究了寡核苷酸双链形成片段之间连接子大小对RNA/DNA、DNA/DNA和RNA/RNA组装体复合物形状和亚基数量的影响。此处总结为热图的复合物类型数据为NA构建体的设计提供了便捷工具。在RNA/DNA、DNA/DNA和RNA/RNA复合物中发现的一般规律不仅有助于设计具有所需结构的复合物,还能有目的地改变其几何形状。通过圆二色性分析证实了所研究的RNA/DNA复合物的双螺旋A构象。此外,我们首次展示了RNase H和咪唑对杂交自限性复合物中RNA的有效降解。这些结果为设计作为纳米技术、纳米机械和生物医学应用工具的超分子复合物开辟了新前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/ddb5dd5e65ef/molecules-29-05896-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/f47c749a48c1/molecules-29-05896-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/73527aabaf10/molecules-29-05896-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/e9da919e292c/molecules-29-05896-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/a5a38285acb5/molecules-29-05896-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/234f0ca24aff/molecules-29-05896-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/0eac15f0e6e7/molecules-29-05896-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/ddb5dd5e65ef/molecules-29-05896-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/f47c749a48c1/molecules-29-05896-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/73527aabaf10/molecules-29-05896-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/e9da919e292c/molecules-29-05896-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/a5a38285acb5/molecules-29-05896-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/234f0ca24aff/molecules-29-05896-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/0eac15f0e6e7/molecules-29-05896-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11677838/ddb5dd5e65ef/molecules-29-05896-g007.jpg

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Molecules. 2023 Dec 19;29(1):10. doi: 10.3390/molecules29010010.
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